ArticleHepatology (Baltimore, Md.)2014
Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review.Immunology letters · 2019Pooled it
- Betulinic acid as a novel AT1R inhibitor: attenuation of liver fibrosis via modulation of endothelial-mesenchymal transition in chronic hepatic injury.Journal of translational medicine · 2025Article
- Curcumol Attenuates Portal Hypertension and Collateral Shunting Via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats.Biochemical genetics · 2025Article
- From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension.Metabolites · 2025Review
- Heterogeneity of primary and metastatic CAFs: From differential treatment outcomes to treatment opportunities (Review).International journal of oncology · 2024Article
- The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.Cancer cell international · 2023Review
- Liver endothelial cells in NAFLD and transition to NASH and HCC.Cellular and molecular life sciences : CMLS · 2023Review
- Altered splicing factor and alternative splicing events in a mouse model of diet- and polychlorinated biphenyl-induced liver disease.Environmental toxicology and pharmacology · 2023Article
- GPCRs and fibroblast heterogeneity in fibroblast-associated diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Review
- Angiotensin receptor blockers might be protective against hepatic steatosis after liver transplantation.BMC gastroenterology · 2023Article
- Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.International journal of general medicine · 2023Article
- Diabetes Mellitus May Exacerbate Liver Injury in Patients with COVID-19: A Single-Center, Observational, Retrospective Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022Article
- Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD.Seminars in liver disease · 2022Review
- Modulation of hepatic stellate cells by MutaflorJournal of translational medicine · 2022Article
- [Study of the negative regulation of transforming growth factor beta type II receptor to inhibit the occurrence and development of liver fibrosis with miR-217].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- Article
- Vasoconstrictor antagonism improves functional and structural vascular alterations and liver damage in rats with early NAFLD.JHEP reports : innovation in hepatology · 2022Article
- Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model.Biomedicines · 2022Article
- Current and investigational drugs in early clinical development for portal hypertension.Frontiers in medicine · 2022Review
- Cirrhosis-Associated RAS-Inflammation-Coagulation Axis Anomalies: Parallels to Severe COVID-19.Journal of personalized medicine · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 3 institutions in 3 countries.
Funding
Abstract
unlabelledActivation of the renin angiotensin system resulting in stimulation of angiotensin-II (AngII) type I receptor (AT1R) is an important factor in the development of liver fibrosis. Here, we investigated the role of Janus kinase 2 (JAK2) as a newly described intracellular effector of AT1R in mediating liver fibrosis. Fibrotic liver samples from rodents and humans were compared to respective controls. Transcription, protein expression, activation, and localization of JAK2 and downstream effectors were analyzed by real-time polymerase chain reaction, western blotting, immunohistochemistry, and confocal microscopy. Experimental fibrosis was induced by bile duct ligation (BDL), CCl4 intoxication, thioacetamide intoxication or continuous AngII infusion. JAK2 was inhibited by AG490. In vitro experiments were performed with primary rodent hepatic stellate cells (HSCs), Kupffer cells (KCs), and hepatocytes as well as primary human and human-derived LX2 cells. JAK2 expression and activity were increased in experimental rodent and human liver fibrosis, specifically in myofibroblastic HSCs. AT1R stimulation in wild-type animals led to activation of HSCs and fibrosis in vivo through phosphorylation of JAK2 and subsequent RhoA/Rho-kinase activation. These effects were prevented in AT1R(-/-) mice. Pharmacological inhibition of JAK2 attenuated liver fibrosis in rodent fibrosis models. In vitro, JAK2 and downstream effectors showed increased expression and activation in activated HSCs, when compared to quiescent HSCs, KCs, and hepatocytes isolated from rodents. In primary human and LX2 cells, AG490 blocked AngII-induced profibrotic gene expression. Overexpression of JAK2 led to increased profibrotic gene expression in LX2 cells, which was blocked by AG490.
conclusionOur study substantiates the important cell-intrinsic role of JAK2 in HSCs for development of liver fibrosis. Inhibition of JAK2 might therefore offer a promising therapy for liver fibrosis.
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