ArticleGastroenterology2009
Fibronectin stimulates endothelin-1 synthesis in rat hepatic myofibroblasts via a Src/ERK-regulated signaling pathway.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
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- Insulin-like growth factor 1 (IGF-1)-induced changes in cardiac inducible nitric oxide synthase (iNOS) in obese rats.Frontiers in endocrinology · 2025Article
- SENP1-Mediated HSP90ab1 DeSUMOylation in Cardiomyocytes Prevents Myocardial Fibrosis by Paracrine Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- In Vivo and In Vitro Models to Study Liver Fibrosis: Mechanisms and Limitations.Cellular and molecular gastroenterology and hepatology · 2023Review
- Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine.The EPMA journal · 2021Review
- Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications.Nature reviews. Cardiology · 2021Review
- Structural and Functional Characterization of Fibronectin in Extracellular Vesicles From Hepatocytes.Frontiers in cell and developmental biology · 2021Article
- Endothelin-1 in portal hypertension: The intricate role of hepatic stellate cells.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Proteasomal Degradation of Enhancer of Zeste Homologue 2 in Cholangiocytes Promotes Biliary Fibrosis.Hepatology (Baltimore, Md.) · 2019Article
- The Molecular Basis of Portal Hypertension.Transactions of the American Clinical and Climatological Association · 2017Review
- Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions.Journal of hepatology · 2014Review
- Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.The Journal of biological chemistry · 2014Article
- Matrix metalloproteinases: drug targets for myocardial infarction.Current drug targets · 2013Review
- Preproendothelin-1 expression is negatively regulated by IFNγ during hepatic stellate cell activation.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Intestinal decontamination inhibits TLR4 dependent fibronectin-mediated cross-talk between stellate cells and endothelial cells in liver fibrosis in mice.Journal of hepatology · 2012Article
- Endothelin and hepatic wound healing.Pharmacological research · 2011Review
- Tumor necrosis factor α stimulates endothelin-1 synthesis in rat hepatic stellate cells in hepatic wound healing through a novel IKK/JNK pathway.Experimental cell research · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsLiver injury serves as an excellent model of wound healing, characterized by increased synthesis of various cytokines and peptides, including the vasoactive peptide endothelin-1. In the liver, wound healing is mediated by effector cells such as hepatic stellate cells, which cause tissue contraction. Endothelin-1 has autocrine effects on stellate cells and induces their contractile activities. We explored the role of various extracellular matrix components, particularly of fibronectin, in regulating endothelin-1 production during liver injury.
methodsHepatic stellate cells were isolated from normal and injured rats. Real-time polymerase chain reaction immunoblot and enzyme-linked immunosorbent assay analyses were used to measure specific variables, including endothelin-1 production. Preproendothelin-1 promoter activity was determined by a luciferase assay. Stellate cell contraction was measured by a gel contraction assay.
resultsFibronectin stimulated transcription of preproendothelin-1 messenger RNA and expression of endothelin through an integrin-dependent pathway in activated hepatic stellate cells. In these cells, fibronectin induced phosphorylation/activation of extracellular signal-regulated kinase (ERK) through a Shc- and Src-dependent mechanism; ERK activation was required for fibronectin-induced endothelin-1 expression. Fibronectin stimulation by stellate cells induced expression of smooth muscle alpha-actin and endothelin-1-mediated autocrine stellate cell contraction. Stellate cells isolated from injured livers of rats exhibited increased basal phosphorylation levels of Src, Shc, and ERK, as well as increased endothelin-1 synthesis.
conclusionsFibronectin stimulates activated stellate cells to produce endothelin-1 and contract, via an ERK-dependent signaling pathway. The resulting autocrine functional effects of endothelin-1 are likely to be important in the wound-healing process in injured liver.
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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.