The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The requested identity is verified. CH25H in Homo sapiens encodes cholesterol 25-hydroxylase (also cholesterol 25-monooxygenase; UniProt O95992), not a similarly named protein from another organism. The original cloning study identified the human enzyme as a 272-amino-acid, polytopic membrane protein; the mouse ortholog is 298 amino acids, a distinction occasionally reversed in secondary summaries. Human and mouse proteins are 78% identical. The human gene is intronless and was mapped to chromosome 10q23. These findings agree with the supplied fatty-acid-hydroxylase/sterol-desaturase-related domain and family annotations. No conflicting same-symbol protein was found. (lund1998cdnacloningof pages 5-6)
CH25H is principally an endoplasmic-reticulum-associated, non-cytochrome-P450, non-heme diiron hydroxylase that hydroxylates the cholesterol side chain at carbon 25 to form 25-hydroxycholesterol (25-HC). Its physiological importance comes less from bulk cholesterol disposal than from generating a potent, mobile oxysterol signal that couples innate immune activation to membrane and sterol homeostasis. Strong direct evidence supports the cholesterol-to-25-HC reaction, membrane integration, ER localization, and essential catalytic histidines. Exact membrane topology, the physiological electron-transfer partner, a comprehensive substrate-selectivity profile, and a high-resolution human structure remain comparatively under-resolved. (liu201825hydroxycholesterolactivatesthe pages 13-16, cao2020multiplerolesof pages 1-2, lund1998cdnacloningof pages 5-6)
| Topic | Best-supported annotation | Evidence type/model | Key caveat |
|---|---|---|---|
| Identity | Human CH25H, UniProt O95992, is cholesterol 25-hydroxylase/cholesterol 25-monooxygenase. The human protein is 272 aa, whereas the mouse protein is 298 aa; the orthologs share 78% identity. (lund1998cdnacloningof pages 5-6) | Human and mouse cDNA cloning, functional expression, and product identification by GC–MS | Some reviews reverse the species lengths; the original cloning study supports human 272 aa and mouse 298 aa. |
| Catalytic reaction | Catalyzes side-chain C25 hydroxylation: cholesterol + O₂ + reducing equivalents → 25-hydroxycholesterol + H₂O. Expressed enzyme generated chemically verified 25-HC. (cao2020multiplerolesof pages 1-2, lund1998cdnacloningof pages 5-6) | Functional expression, biochemical product identification, and enzymology review | The physiological electron donor and complete reaction stoichiometry were not firmly resolved in the retrieved evidence; other enzymes can generate smaller amounts of 25-HC. |
| Family, cofactor, and motifs | Non-heme, diiron-dependent membrane hydroxylase of the sterol-desaturase/fatty-acid-hydroxylase family, containing three conserved histidine clusters implicated in catalysis. Replacing two histidines in the third mouse cluster abolished activity without reducing protein abundance. (cao2020multiplerolesof pages 1-2, lund1998cdnacloningof pages 5-6) | Sequence comparison and site-directed mutagenesis | The reported mutagenesis positions are from mouse CH25H; no high-resolution human CH25H structure was established in the retrieved evidence. |
| Localization and topology | Predominantly an ER-associated polytopic membrane protein. Membrane fractionation and glycosylation supported membrane integration; human HepG2 imaging showed colocalization with ER marker HSPA5 rather than plasma-membrane ATP1A1. Golgi localization has also been reported. (liu201825hydroxycholesterolactivatesthe pages 13-16, zhao2020multifacetedfunctionsof pages 1-3, lund1998cdnacloningof pages 5-6) | Transfected-protein fractionation and glycosylation; human-cell immunofluorescence | The exact transmembrane-segment count and catalytic orientation are less certain than ER localization. |
| SREBP–SCAP–INSIG and HMGCR | 25-HC stabilizes INSIG–SCAP/SREBP-2 retention in the ER, preventing Golgi processing of SREBP-2. It also promotes INSIG-dependent HMGCR ubiquitination and degradation, reducing cholesterol synthesis and LDL uptake. (liu201825hydroxycholesterolactivatesthe pages 20-23, nguyen202425hydroxycholesterolinhealth pages 5-6) | Mechanistic cell studies summarized in primary literature and a 2024 JLR review | Canonical SREBP effects were not detected in lipid-loaded plaque macrophages in the 2023 atherosclerosis study, indicating context dependence. |
| LXR and cholesterol trafficking | 25-HC can activate LXRα/β, inducing cholesterol-efflux genes including ABCA1 and ABCG1. LXR agonism can also increase CH25H transcription through human-promoter LXREs, creating positive feedback. (liu201825hydroxycholesterolactivatesthe pages 1-4, liu201825hydroxycholesterolactivatesthe pages 4-6) | Human HepG2 promoter and cell experiments; mouse macrophage and in-vivo validation | Important inflammatory and vascular effects of 25-HC can occur independently of LXR. |
| Immune induction and antiviral action | CH25H is an interferon-stimulated gene. Interferons, viral infection, and TLR4/LPS signaling induce CH25H and 25-HC; 25-HC restricts diverse viruses through context-dependent effects on cholesterol organization, viral entry or fusion, replication membranes, LXR/SREBP signaling, and cellular stress responses. (nguyen202425hydroxycholesterolinhealth pages 5-6, liu201825hydroxycholesterolactivatesthe pages 4-6, zhao2020multifacetedfunctionsof pages 1-3) | Human and animal cells, infection models, and reviews | Mechanisms vary by virus and cell type; exogenous 25-HC treatment does not necessarily reproduce endogenous CH25H biology. |
| Atherosclerosis, 2023 | Human coronary plaques contained 25-HC, with CH25H enriched in inflammatory macrophages. In Ch25h-null bone-marrow → Ldlr-null mice, 12 weeks of Western diet produced less atherosclerosis and necrosis and more stable plaques. The mechanism involved accessible plasma-membrane cholesterol, TLR4/NF-κB signaling, apoptosis/efferocytosis, and impaired smooth-muscle migration rather than LXR/SREBP. Human sampling included 6 mild, 6 moderate, and 4 severe lesions. (canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 3-4, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 1-3, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 23-27) | Human plaque lipidomics and single-cell localization; mouse genetics, bone-marrow transplantation, and cell assays | Human evidence is associative; causal and intervention evidence is primarily murine. |
| Acute lung injury and ARDS, 2023 | Ch25h loss protected mice from inflammatory endothelial leak; 25-HC induced ER stress, disrupted endothelial barrier function, and acted largely independently of LXR. In ARDS, alveolar-macrophage CH25H (n=30) and BAL-fluid 25-HC (n=81) correlated with vascular-leak markers, worse oxygenation, inflammation, and clinical severity. (madenspacher202325hydroxycholesterolexacerbatesvascular pages 4-5, madenspacher202325hydroxycholesterolexacerbatesvascular pages 2-4, madenspacher202325hydroxycholesterolexacerbatesvascular pages 5-7) | Mouse knockout and injury models, endothelial assays, and observational human ARDS cohorts | Human correlations do not establish causality; effects may differ by cell type and phase of inflammation. |
| Translational status | CH25H expression and 25-HC are being investigated as biomarkers and pathway-level targets in atherosclerosis, ARDS, inflammatory disease, and viral infection. (canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 3-4, madenspacher202325hydroxycholesterolexacerbatesvascular pages 1-2, madenspacher202325hydroxycholesterolexacerbatesvascular pages 5-7) | Preclinical genetic and pharmacological studies plus observational human samples | No established CH25H-directed therapy or validated clinical indication was identified; systemic inhibition or supplementation may be risky because 25-HC can be antiviral, proinflammatory, or pro-resolving depending on context. |
Table: Compact evidence map for human CH25H identity, enzymology, localization, pathways, recent disease studies, and translational maturity. It distinguishes direct human observations from cell and mouse-model evidence while highlighting unresolved issues.
The primary cloning and functional-expression evidence establishes that the human gene encodes an active cholesterol 25-hydroxylase. Expression produced a sterol identified as 25-HC by gas chromatography–mass spectrometry. The protein is therefore correctly annotated as cholesterol 25-hydroxylase/cholesterol 25-monooxygenase, rather than inferred merely from sequence similarity. [Lund et al., Journal of Biological Chemistry, 18 December 1998; DOI/URL: https://doi.org/10.1074/jbc.273.51.34316]. (lund1998cdnacloningof pages 5-6)
The supplied InterPro/Pfam assignments—Fatty_acid_hydroxylase, sterol-desaturase-related, and FA_hydroxylase—fit the experimentally supported classification. CH25H belongs to a small group of membrane-bound, histidine-ligated diiron enzymes acting on hydrophobic substrates. It is mechanistically distinct from heme-containing cytochrome-P450 sterol hydroxylases. Other enzymes, including CYP3A4, CYP27A1 and CYP46A1, can produce some 25-HC, but available reviews regard their quantitative in-vivo contribution as less well established than inducible CH25H production in immune contexts. (nguyen202425hydroxycholesterolinhealth pages 5-6, cao2020multiplerolesof pages 1-2)
The core reaction is side-chain C25 hydroxylation:
cholesterol + O₂ + reducing equivalents → 25-hydroxycholesterol + H₂O.
This converts the terminally branched cholesterol side chain into the oxysterol 25-HC. The EC annotation supplied by the user is EC 1.14.99.38. Functional expression and chemical identification provide direct evidence for product formation. Oxygen and a diiron center are required conceptually for monooxygenation, but the retrieved primary evidence does not firmly identify the physiological reductase/electron donor or establish complete purified-enzyme stoichiometry. These details should therefore not be over-annotated by analogy to better-characterized desaturases. (cao2020multiplerolesof pages 1-2, lund1998cdnacloningof pages 5-6)
CH25H contains three conserved histidine-rich clusters characteristic of membrane diiron hydroxylases. In the mouse ortholog, substitution of His242 and His243 with glutamine abolished hydroxylase activity without reducing steady-state protein abundance. This separates catalytic loss from protein instability and strongly implicates the histidine cluster in coordinating the metal center or supporting catalysis. The residue numbering is from mouse CH25H and should not be transferred uncritically to the shorter human sequence. (lund1998cdnacloningof pages 5-6)
The best-established physiological substrate is cholesterol, and the defining product is 25-HC. The available evidence does not establish that human CH25H is absolutely cholesterol-specific, because a modern purified-enzyme kinetic comparison across sterols was not recovered. Accordingly, a defensible annotation is “cholesterol-preferring/physiological cholesterol 25-hydroxylase,” rather than a claim of exclusive specificity. The presence of 25-HC from alternative enzymatic and nonenzymatic routes also means that measured 25-HC is not automatically proof of CH25H activity unless genetic, expression, or isotope-tracing evidence is included. (nguyen202425hydroxycholesterolinhealth pages 5-6, cao2020multiplerolesof pages 1-2)
CH25H carries out its primary reaction in intracellular membranes, predominantly the endoplasmic reticulum. The original work described a polytopic membrane protein and found it in membrane fractions; hydropathy and glycosylation experiments supported membrane integration. In human HepG2 cells, immunofluorescence showed colocalization with the ER marker HSPA5 rather than the plasma-membrane marker ATP1A1. Golgi association has also been reported, but ER localization has the strongest mechanistic support. (liu201825hydroxycholesterolactivatesthe pages 13-16, zhao2020multifacetedfunctionsof pages 1-3, lund1998cdnacloningof pages 5-6)
This location is functionally coherent: both cholesterol substrate and the SCAP–SREBP–INSIG cholesterol-sensing apparatus reside in or traffic through ER membranes. The exact number and orientation of transmembrane helices, and which membrane face contains the catalytic center, are less securely established by the retrieved evidence than the broader conclusion that CH25H is an ER-integrated enzyme.
Although CH25H itself is membrane-bound, 25-HC is mobile. It can redistribute among cellular membranes and can be secreted by activated macrophages, permitting autocrine and paracrine actions. Thus, CH25H’s catalytic site is intracellular, while the biological field of action of its product extends to other membranes and neighboring cells. Activated plaque macrophages, for example, secreted 25-HC, which affected vascular smooth-muscle-cell migration. (canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 9-11, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 13-14)
CH25H is generally expressed at low basal levels but is strongly inducible. A 2024 authoritative review reports expression across hematopoietic, epithelial, endothelial, macrophage and lymphoid populations, with relatively high Human Protein Atlas signals in adipose tissue, lung, urinary bladder and gallbladder. CNS expression has been reported in microglia, astrocytes and blood–brain-barrier endothelial cells. These atlas-level patterns are useful for prioritization but are less definitive than cell-specific protein and metabolite measurements. [Nguyen et al., Journal of Lipid Research, January 2024; DOI/URL: https://doi.org/10.1016/j.jlr.2023.100486]. (nguyen202425hydroxycholesterolinhealth pages 5-6)
CH25H is an interferon-stimulated gene. Viral infection, interferons, and TLR stimulation—particularly LPS through TLR4/TRIF in macrophages—can rapidly increase its transcription and 25-HC production. Human experimental endotoxemia has produced a transient rise in circulating 25-HC, supporting operation of this inducible pathway in humans rather than only in mice. In model systems, inflammatory cytokines and STAT1 can contribute, while ATF3 can repress transcription. (liu201825hydroxycholesterolactivatesthe pages 20-23, nguyen202425hydroxycholesterolinhealth pages 5-6, cao2020multiplerolesof pages 1-2)
A second regulatory route involves LXR. Several LXR-response elements were identified in the human CH25H promoter. In HepG2 cells, 25-HC and synthetic LXR agonists increased CH25H mRNA and protein; LXRα or LXRβ overexpression enhanced this response, whereas receptor inhibition attenuated it. Mouse macrophage and in-vivo agonist experiments supported the same pathway. This creates a possible positive-feedback circuit—25-HC activates LXR, which can increase CH25H—but its magnitude is cell- and context-dependent. [Liu et al., Journal of Lipid Research, March 2018; DOI/URL: https://doi.org/10.1194/jlr.M080440]. (liu201825hydroxycholesterolactivatesthe pages 1-4, liu201825hydroxycholesterolactivatesthe pages 13-16)
25-HC promotes association of INSIG proteins with the SCAP–SREBP complex in the ER. This prevents SCAP-mediated transport of SREBP, particularly SREBP2, to the Golgi, where activating proteolysis would normally occur. Reduced nuclear SREBP2 lowers transcription of cholesterol-biosynthetic and uptake genes, including HMGCR and LDLR. 25-HC also promotes INSIG-dependent HMGCR ubiquitination and degradation. Together, these actions reduce de-novo cholesterol synthesis and LDL uptake. (liu201825hydroxycholesterolactivatesthe pages 20-23, nguyen202425hydroxycholesterolinhealth pages 5-6)
25-HC can additionally activate acyl-CoA:cholesterol acyltransferase activity, increasing conversion of free cholesterol to cholesteryl esters. The integrated effect is therefore to reduce the accessible free-cholesterol pool through suppressed synthesis, accelerated HMGCR loss, and enhanced storage. (liu201825hydroxycholesterolactivatesthe pages 4-6)
25-HC can act as an endogenous ligand for LXRα/β. LXR activation induces cholesterol-export machinery, including ABCA1 and ABCG1, promoting efflux to extracellular acceptors. This complements SREBP inhibition: one pathway decreases supply and uptake, while the other increases disposal from cells. Nevertheless, 25-HC concentration, metabolism, receptor availability and cell state determine whether LXR signaling dominates. (liu201825hydroxycholesterolactivatesthe pages 4-6)
CYP7B1 converts 25-HC to 7α,25-dihydroxycholesterol, a distinct immune oxysterol. This is important for functional annotation because phenotypes downstream of CH25H need not be mediated directly by 25-HC; some can reflect its metabolites. Likewise, sulfation to 25-HC-3-sulfate changes biological activity. (nguyen202425hydroxycholesterolinhealth pages 5-6)
Interferon-induced CH25H and 25-HC restrict diverse enveloped and non-enveloped viruses in experimental systems. Proposed mechanisms include changing accessible membrane cholesterol and thereby inhibiting viral entry/fusion; disrupting cholesterol-dependent replication organelles; suppressing SREBP-dependent lipid synthesis; engaging LXR pathways; and activating cellular stress responses. Reviews emphasize that the dominant mechanism varies by virus, target cell and timing. Reported susceptible viruses include HIV, Ebola, Nipah, Rift Valley fever and Zika viruses. (zhao2020multifacetedfunctionsof pages 1-3)
The pathway is therefore best understood as an inducible immunometabolic restriction mechanism, not as a conventional virus-specific effector. Exogenous micromolar 25-HC can also have effects that endogenous, membrane-localized CH25H production does not reproduce; therapeutic conclusions based solely on adding 25-HC to culture require caution.
25-HC can be anti-inflammatory or pro-inflammatory depending on context. Canonical SREBP inhibition may limit inflammasome and IL-1-family responses in some macrophage systems, whereas membrane-cholesterol remodeling can enhance TLR signaling in lipid-loaded macrophages. This apparent contradiction is now considered a central biological feature rather than merely inconsistent literature. (liu201825hydroxycholesterolactivatesthe pages 4-6, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 3-4, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 13-14)
A January 2023 Circulation study found that 25-HC accumulated with severity in human coronary atherosclerotic lesions and that CH25H was enriched in inflammatory plaque macrophages. Human biochemical sampling comprised 6 mild, 6 moderate and 4 severe lesions. In Ldlr-null mice receiving wild-type or Ch25h-null bone marrow followed by 12 weeks of Western diet, hematopoietic Ch25h deficiency reduced lesion burden, necrotic-core area and macrophage accumulation while increasing collagen and smooth-muscle-cell features associated with plaque stability. Several endpoints used n=10–14 mice per group. [Canfrán-Duque et al., Circulation 147:388–408, 31 January 2023; DOI/URL: https://doi.org/10.1161/CIRCULATIONAHA.122.059062]. (canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 4-6, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 1-3, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 23-27)
Mechanistically, the effect differed from the textbook SREBP/LXR model. In lipid-loaded macrophages, CH25H-derived 25-HC maintained accessible plasma-membrane cholesterol and amplified TLR4–NF-κB signaling. Ch25h deficiency reduced p65, p38 and IRF3 pathway activation, improved efferocytosis and resistance to apoptosis, and shifted transcription toward pro-resolving programs. RNA sequencing identified approximately 200 differential genes at baseline, more than 500 after four hours of LPS, and 552 after 12 hours, using a 1.5-fold threshold and P≤0.05. Secreted 25-HC also inhibited smooth-muscle migration; one assay used 5 μM 25-HC with 10 ng/mL PDGF-BB. (canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 30-34, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 9-11, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 6-8)
The expert interpretation is that CH25H can control inflammation by reorganizing membrane cholesterol independently of measurable SREBP or LXR transcriptional effects. Human plaque findings support relevance, but causal evidence and apparent therapeutic benefit of deletion remain murine.
A 2023 JCI Insight study identified a largely LXR-independent, detrimental role for CH25H/25-HC in inflammatory lung vascular leak. In mouse models, Ch25h deletion reduced bronchoalveolar protein, albumin, IgM, inflammatory cytokines and endothelial activation after high-dose inhaled LPS (3 mg/mL) and after Klebsiella pneumoniae infection, without increasing airway or blood bacterial burden in the latter model. LPS induced Ch25h in pulmonary endothelial cells; 25-HC disrupted VE-cadherin, decreased transendothelial electrical resistance and activated ER-stress markers. The chemical chaperone 4-phenylbutyrate reduced leakage, connecting ER stress mechanistically to barrier failure. [Madenspacher et al., JCI Insight, April 2023; DOI/URL: https://doi.org/10.1172/jci.insight.155448]. (madenspacher202325hydroxycholesterolexacerbatesvascular pages 4-5, madenspacher202325hydroxycholesterolexacerbatesvascular pages 2-4)
Human observations strengthened translational relevance: alveolar-macrophage CH25H was measured in 30 ARDS patients, and bronchoalveolar-lavage 25-HC in 81 patients. Both associated with total protein and von Willebrand factor; higher values also tracked with worse oxygenation, higher lung-injury scores and increased IL-8, IL-6 and IL-17A. Associations persisted after adjustment for APACHE II score, age, sex and treatment group. These data support biomarker potential but remain observational and cannot prove that inhibiting CH25H would improve human ARDS. (madenspacher202325hydroxycholesterolexacerbatesvascular pages 5-7)
The January 2024 Journal of Lipid Research review concludes that 25-HC is best viewed as a context-dependent integrator of cholesterol homeostasis, immunity and disease. Its effects can involve SCAP/SREBP2, HMGCR degradation, LXR, downstream conversion to 7α,25-dihydroxycholesterol, membrane biophysics and stress signaling. The review also highlights apparently opposing antiviral and inflammatory observations, reinforcing the need to specify cell type, disease phase, concentration and whether 25-HC is endogenous or experimentally added. (nguyen202425hydroxycholesterolinhealth pages 5-6)
High-confidence annotation: exact human identity; cholesterol-to-25-HC activity; non-P450 diiron/histidine-dependent mechanism; polytopic ER membrane localization; inducibility by innate immune signals; and potent regulation of cellular sterol handling. These conclusions have convergent cloning, functional-expression, mutagenesis, imaging and metabolite evidence. (nguyen202425hydroxycholesterolinhealth pages 5-6, liu201825hydroxycholesterolactivatesthe pages 13-16, lund1998cdnacloningof pages 5-6)
Moderate-confidence, context-dependent annotation: LXR feedback, antiviral mechanisms, inflammasome control, and tissue-specific inflammatory outputs. These are supported experimentally but vary among cell types, stimuli and concentrations. (liu201825hydroxycholesterolactivatesthe pages 1-4, liu201825hydroxycholesterolactivatesthe pages 4-6, zhao2020multifacetedfunctionsof pages 1-3)
Emerging translational claims: causal promotion of atherosclerosis and lung vascular leak is compelling in genetic mouse models, while available human evidence is associative. The pathway should therefore be described as a promising biomarker and intervention target, not a clinically validated target. (canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 3-4, canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 1-3, madenspacher202325hydroxycholesterolexacerbatesvascular pages 5-7)
The most important conceptual distinction is between CH25H’s direct enzymatic function and the many actions of its product. CH25H directly hydroxylates cholesterol in intracellular membranes. SREBP retention, HMGCR degradation, LXR activation, altered membrane accessibility, antiviral restriction, ER stress and paracrine vascular effects are downstream functions of 25-HC or its metabolites. Assigning all such effects as intrinsic protein activities would be mechanistically inaccurate.
Human CH25H/O95992 is securely annotated as an inducible, ER-integrated diiron cholesterol 25-hydroxylase whose principal reaction produces 25-HC. Its key biological role is to translate sterol and innate-immune signals into rapid control of cholesterol synthesis, storage, export and membrane organization. Recent 2023–2024 work expands this model: CH25H-derived 25-HC can drive plaque inflammation and lung endothelial leak through membrane and ER-stress mechanisms that are not reducible to canonical LXR/SREBP signaling. The pathway has credible biomarker and therapeutic-target potential, but its strongly cell-, disease- and time-dependent effects currently argue against indiscriminate systemic activation or inhibition.
References
(lund1998cdnacloningof pages 5-6): Erik G. Lund, Thomas A. Kerr, Juro Sakai, Wei-Ping Li, and David W. Russell. Cdna cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism*. The Journal of Biological Chemistry, 273:34316-34327, Dec 1998. URL: https://doi.org/10.1074/jbc.273.51.34316, doi:10.1074/jbc.273.51.34316. This article has 429 citations.
(liu201825hydroxycholesterolactivatesthe pages 13-16): Ying Liu, Zhuo Wei, Xingzhe Ma, Xiaoxiao Yang, Yuanli Chen, Lei Sun, Chuanrui Ma, Qing R. Miao, David P. Hajjar, Jihong Han, and Yajun Duan. 25-hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an lxr-dependent mechanism. Mar 2018. URL: https://doi.org/10.1194/jlr.m080440, doi:10.1194/jlr.m080440. This article has 93 citations and is from a peer-reviewed journal.
(cao2020multiplerolesof pages 1-2): Qin Cao, Zhongzhong Liu, Yan Xiong, Zibiao Zhong, and Qifa Ye. Multiple roles of 25-hydroxycholesterol in lipid metabolism, antivirus process, inflammatory response, and cell survival. Oxidative Medicine and Cellular Longevity, 2020:1-11, Nov 2020. URL: https://doi.org/10.1155/2020/8893305, doi:10.1155/2020/8893305. This article has 60 citations.
(zhao2020multifacetedfunctionsof pages 1-3): Jin Zhao, Jiaoshan Chen, Minchao Li, Musha Chen, and Caijun Sun. Multifaceted functions of ch25h and 25hc to modulate the lipid metabolism, immune responses, and broadly antiviral activities. Jul 2020. URL: https://doi.org/10.3390/v12070727, doi:10.3390/v12070727. This article has 116 citations.
(liu201825hydroxycholesterolactivatesthe pages 20-23): Ying Liu, Zhuo Wei, Xingzhe Ma, Xiaoxiao Yang, Yuanli Chen, Lei Sun, Chuanrui Ma, Qing R. Miao, David P. Hajjar, Jihong Han, and Yajun Duan. 25-hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an lxr-dependent mechanism. Mar 2018. URL: https://doi.org/10.1194/jlr.m080440, doi:10.1194/jlr.m080440. This article has 93 citations and is from a peer-reviewed journal.
(nguyen202425hydroxycholesterolinhealth pages 5-6): Cindy Nguyen, Julien Saint-Pol, Shiraz Dib, Caroline Pot, and Fabien Gosselet. 25-hydroxycholesterol in health and diseases. Jan 2024. URL: https://doi.org/10.1016/j.jlr.2023.100486, doi:10.1016/j.jlr.2023.100486. This article has 61 citations and is from a peer-reviewed journal.
(liu201825hydroxycholesterolactivatesthe pages 1-4): Ying Liu, Zhuo Wei, Xingzhe Ma, Xiaoxiao Yang, Yuanli Chen, Lei Sun, Chuanrui Ma, Qing R. Miao, David P. Hajjar, Jihong Han, and Yajun Duan. 25-hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an lxr-dependent mechanism. Mar 2018. URL: https://doi.org/10.1194/jlr.m080440, doi:10.1194/jlr.m080440. This article has 93 citations and is from a peer-reviewed journal.
(liu201825hydroxycholesterolactivatesthe pages 4-6): Ying Liu, Zhuo Wei, Xingzhe Ma, Xiaoxiao Yang, Yuanli Chen, Lei Sun, Chuanrui Ma, Qing R. Miao, David P. Hajjar, Jihong Han, and Yajun Duan. 25-hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an lxr-dependent mechanism. Mar 2018. URL: https://doi.org/10.1194/jlr.m080440, doi:10.1194/jlr.m080440. This article has 93 citations and is from a peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 3-4): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 1-3): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 23-27): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(madenspacher202325hydroxycholesterolexacerbatesvascular pages 4-5): Jennifer H. Madenspacher, Eric D. Morrell, Jeffrey G. McDonald, Bonne M. Thompson, Yue Li, Konstantin G. Birukov, Anna A. Birukova, Renee D. Stapleton, Aidin Alejo, Peer W. Karmaus, Julie M. Meacham, Prashant Rai, Carmen Mikacenic, Mark M. Wurfel, and Michael B. Fessler. 25-hydroxycholesterol exacerbates vascular leak during acute lung injury. Apr 2023. URL: https://doi.org/10.1172/jci.insight.155448, doi:10.1172/jci.insight.155448. This article has 27 citations and is from a domain leading peer-reviewed journal.
(madenspacher202325hydroxycholesterolexacerbatesvascular pages 2-4): Jennifer H. Madenspacher, Eric D. Morrell, Jeffrey G. McDonald, Bonne M. Thompson, Yue Li, Konstantin G. Birukov, Anna A. Birukova, Renee D. Stapleton, Aidin Alejo, Peer W. Karmaus, Julie M. Meacham, Prashant Rai, Carmen Mikacenic, Mark M. Wurfel, and Michael B. Fessler. 25-hydroxycholesterol exacerbates vascular leak during acute lung injury. Apr 2023. URL: https://doi.org/10.1172/jci.insight.155448, doi:10.1172/jci.insight.155448. This article has 27 citations and is from a domain leading peer-reviewed journal.
(madenspacher202325hydroxycholesterolexacerbatesvascular pages 5-7): Jennifer H. Madenspacher, Eric D. Morrell, Jeffrey G. McDonald, Bonne M. Thompson, Yue Li, Konstantin G. Birukov, Anna A. Birukova, Renee D. Stapleton, Aidin Alejo, Peer W. Karmaus, Julie M. Meacham, Prashant Rai, Carmen Mikacenic, Mark M. Wurfel, and Michael B. Fessler. 25-hydroxycholesterol exacerbates vascular leak during acute lung injury. Apr 2023. URL: https://doi.org/10.1172/jci.insight.155448, doi:10.1172/jci.insight.155448. This article has 27 citations and is from a domain leading peer-reviewed journal.
(madenspacher202325hydroxycholesterolexacerbatesvascular pages 1-2): Jennifer H. Madenspacher, Eric D. Morrell, Jeffrey G. McDonald, Bonne M. Thompson, Yue Li, Konstantin G. Birukov, Anna A. Birukova, Renee D. Stapleton, Aidin Alejo, Peer W. Karmaus, Julie M. Meacham, Prashant Rai, Carmen Mikacenic, Mark M. Wurfel, and Michael B. Fessler. 25-hydroxycholesterol exacerbates vascular leak during acute lung injury. Apr 2023. URL: https://doi.org/10.1172/jci.insight.155448, doi:10.1172/jci.insight.155448. This article has 27 citations and is from a domain leading peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 9-11): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 13-14): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 4-6): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 30-34): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.
(canfranduque2023macrophagederived25hydroxycholesterolpromotes pages 6-8): Alberto Canfrán-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andrés-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernández-Fuertes, Joseph W. Fowler, Diego Gómez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernández-Hernando, and Yajaira Suárez. Macrophage-derived 25-hydroxycholesterol promotes vascular inflammation, atherogenesis, and lesion remodeling. Circulation, 147:388-408, Jan 2023. URL: https://doi.org/10.1161/circulationaha.122.059062, doi:10.1161/circulationaha.122.059062. This article has 139 citations and is from a highest quality peer-reviewed journal.