ArticleJournal of autoimmunity2015
Treatment of cholestatic fibrosis by altering gene expression of Cthrc1: Implications for autoimmune and non-autoimmune liver disease.
Article in Journal of autoimmunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Potential role of CTHRC1 in renal fibrosis.Molecular biology reports · 2026Review
- Collagen Triple Helix Repeat Containing 1 (CTHRC1) in the Nervous System: Expression, Signaling Mechanisms, and Functional Implications.Journal of molecular neuroscience : MN · 2026Review
- Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease.Annals of the rheumatic diseases · 2026Article
- Mitochondrial mGPDH Modulates Fibroblast Function in Diabetic Wound Healing via the SIRT1-c-Myc-TGF-β1 Axis.Diabetes · 2026Article
- Meox1 Promotes Cardiac Fibrosis and Pathological Remodeling following Myocardial Infarction through Cthrc1/p-Smad2/3 Signaling.International journal of biological sciences · 2026Article
- Predicting key gene related to immune infiltration and myofibroblast-like valve interstitial cells in patients with calcified aortic valve disease based on bioinformatics analysis.Journal of thoracic disease · 2023Article
- CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review).Oncology letters · 2023Review
- Collagen Triple Helix Repeat Containing 1 Deficiency Protects Against Airway Remodeling and Inflammation in Asthma Models In Vivo and In Vitro.Inflammation · 2023Article
- CTHRC1 is associated with immune cell infiltration and functions as an adverse marker for prognosis in head and neck squamous cell carcinoma.Oncology letters · 2023Article
- Cthrc1 deficiency aggravates wound healing and promotes cardiac rupture after myocardial infarction via non-canonical WNT5A signaling pathway.International journal of biological sciences · 2023Article
- Gene Therapy for Acquired and Genetic Cholestasis.Biomedicines · 2022Review
- GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1.Nature communications · 2021Article
- Collagen triple helix repeat containing-1 exerts antifibrotic effects on human skin fibroblast and bleomycin-induced dermal fibrosis models.Annals of translational medicine · 2021Article
- The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis.International journal of molecular sciences · 2021Review
- TGF-β Pathway in Salivary Gland Fibrosis.International journal of molecular sciences · 2020Review
- The Distribution and Localization of Collagen Triple Helix Repeat Containing-1 in Naturally and Experimentally Avian Leukosis Virus Subgroup J-Infected Chickens.Frontiers in veterinary science · 2020Article
- Autocrine CTHRC1 activates hepatic stellate cells and promotes liver fibrosis by activating TGF-β signaling.EBioMedicine · 2019Article
- CTHRC1 overexpression predicts poor survival and enhances epithelial-mesenchymal transition in colorectal cancer.Cancer medicine · 2018Article
- Increased Cthrc1 Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-β/Smad Signal Pathway and Modulating YAP Subcellular Location.Current medical science · 2018Article
- An integrated analysis of genome-wide DNA methylation and gene expression data in hepatocellular carcinoma.FEBS open bio · 2018Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Collagen triple helix repeat containing-1 (Cthrc1) is a documented specific inhibitor of TGF-β signaling. Based on this observation, we developed the hypothesis that knocking in/knocking out the Cthrc1 gene in murine models of cholestasis would alter the natural history of cholestatic fibrosis. To study this thesis, we studied two murine models of fibrosis, first, common bile duct ligation (CBDL) and second, feeding of 3, 5-diethoxy-carbonyl-1, 4-dihydrocollidine (DDC). In both models, we administered well-defined adenoviral vectors that expressed either Cthrc1 or, alternatively, a short hairpin RNA (shRNA)-targeting Cthrc1 either before or after establishment of fibrosis. Importantly, when Cthrc1 gene expression was enhanced, we noted a significant improvement of hepatic fibrosis, both microscopically and by analysis of fibrotic gene expression. In contrast, when Cthrc1 gene expression was deleted, there was a significant exacerbation of fibrosis. To identify the mechanism of action of these significant effects produced by knocking in/knocking out Cthrc gene expression, we thence studied the interaction of Cthrc1 gene expression using hepatic stellate cells (HSCs) and human LX-2 cells. Importantly, we demonstrate that Cthrc1 is induced by TGF-β1 via phospho-Smad3 binding to the promoter with subsequent transcription activation. In addition, we demonstrate that Cthrc1 inhibits TGF-β signaling by accelerating degradation of phospho-Smad3 through a proteosomal pathway. Importantly, the anti-fibrotic effects can be recapitulated with a truncated fragment of Cthrc1. In conclusion, our findings uncover a critical negative feedback regulatory loop in which TGF-β1 induces Cthrc1, which can attenuate fibrosis by accelerating degradation of phospho-Smad3.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.