ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
Preproendothelin-1 expression is negatively regulated by IFNγ during hepatic stellate cell activation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- High throughput interrogation of human liver stellate cells reveals microenvironmental regulation of phenotype.Acta biomaterialia · 2022Pooled it
- The cellular microenvironment and cytoskeletal actin dynamics in liver fibrogenesis.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2022Article
- Role of hepatic stellate cells in liver ischemia-reperfusion injury.Frontiers in immunology · 2022Review
- Endothelin-1 in portal hypertension: The intricate role of hepatic stellate cells.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation.British journal of haematology · 2020Review
- Crosstalk network among multiple inflammatory mediators in liver fibrosis.World journal of gastroenterology · 2019Review
- Systems Biology Analyses Show Hyperactivation of Transforming Growth Factor-β and JNK Signaling Pathways in Esophageal Cancer.Gastroenterology · 2019Article
- Upregulation of the actin cytoskeleton via myocardin leads to increased expression of type 1 collagen.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Hepatic stellate cells as key target in liver fibrosis.Advanced drug delivery reviews · 2017Review
- The Molecular Basis of Portal Hypertension.Transactions of the American Clinical and Climatological Association · 2017Review
- Eggshell membrane ameliorates hepatic fibrogenesis in human C3A cells and rats through changes in PPARγ-Endothelin 1 signaling.Scientific reports · 2014Article
- Tissue-specific and time-dependent regulation of the endothelin axis by the circadian clock protein Per1.Life sciences · 2014Article
- Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.PloS one · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Endothelin-1 (ET-1), a powerful vasoconstrictor peptide, is produced by activated hepatic stellate cells (HSC) and promotes cell proliferation, fibrogenesis, and contraction, the latter of which has been thought to be mechanistically linked to portal hypertension in cirrhosis. Interferon-γ (IFNγ), a Th1 cytokine produced by T cells, inhibits stellate cell proliferation, fibrogenesis, and muscle-specific gene expression. Whether IFNγ-induced inhibitory effects are linked to regulation of ET-1 expression in activated stellate cells remains unknown. Here we examined IFNγ's effects on preproET-1 mRNA expression and the signaling pathways underlying this process. We demonstrated that preproET-1 mRNA expression in HSCs was prominently increased during cell culture-induced activation; IFNγ significantly inhibited both preproET-1 mRNA expression and ET-1 peptide production. Similar results were found in an in vivo model of liver injury and intraperitoneal administration of IFNγ. PreproET-1 promoter analysis revealed that IFNγ-induced inhibition of preproET-1 mRNA expression was closely linked to the AP-1 and Smad3 signaling pathways. Furthermore, IFNγ reduced JNK phosphorylation, which tightly was associated with decreased phosphorylation of downstream factors c-Jun and Smad3 and decreased binding activity of c-Jun and Smad3 in the preprpET-1 promoter. Importantly, IFNγ reduced both c-Jun mRNA and protein levels. Given the important role of ET-1 in wound healing, our results suggest a novel negative signaling network by which IFNγ inhibits preproET-1 expression, highlighting one potential molecular mechanism for IFNγ-induced host immunomodulation of liver fibrogenesis.
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Registered trials
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