ArticleJournal of cellular and molecular medicine2008
Activation of TGF-beta within cultured hepatocytes and in liver injury leads to intracrine signaling with expression of connective tissue growth factor.
Article in Journal of cellular and molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 58 citations in OpenAlex.
- Adipose tissue depot specific expression and regulation of fibrosis-related genes and proteins in experimental obesity.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- A model for the dissemination of circulating tumour cell clusters involving platelet recruitment and a plastic switch between cooperative and individual behaviours.BMC ecology and evolution · 2023Article
- [Calpain activation promotes dialysis-associated peritoneal fibrosis in rats].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Biomaterial-based cell delivery strategies to promote liver regeneration.Biomaterials research · 2021Review
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- The small molecule drug diminazene aceturate inhibits liver injury and biliary fibrosis in mice.Scientific reports · 2018Article
- Calpain inhibition attenuates bleomycin-induced pulmonary fibrosis via switching the development of epithelial-mesenchymal transition.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease.Protein & cell · 2017Review
- Article
- A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice.Scientific reports · 2016Article
- Calpain-2 activates Akt via TGF-β1-mTORC2 pathway in pulmonary artery smooth muscle cells.American journal of physiology. Cell physiology · 2016Article
- Role of Smad3 in platelet-derived growth factor-C-induced liver fibrosis.American journal of physiology. Cell physiology · 2016Article
- Effects of connective tissue growth factor (CTGF) gene silencing on the radiosensitivity of glioblastoma.International journal of clinical and experimental medicine · 2014Article
- Differential hepatoprotective mechanisms of rutin and quercetin in CCl(4)-intoxicated BALB/cN mice.Acta pharmacologica Sinica · 2012Article
- Calpain mediates pulmonary vascular remodeling in rodent models of pulmonary hypertension, and its inhibition attenuates pathologic features of disease.The Journal of clinical investigation · 2011Article
- Coffee prevents CCl(4)-induced liver cirrhosis in the rat.Hepatology international · 2011Article
- A local proinflammatory signalling loop facilitates adverse age-associated arterial remodeling.PloS one · 2011Article
- Connective tissue growth factor reacts as an IL-6/STAT3-regulated hepatic negative acute phase protein.World journal of gastroenterology · 2011Article
- The role of connective tissue growth factor (CTGF/CCN2) in skeletogenesis.Critical reviews in eukaryotic gene expression · 2011Review
- Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms.Liver international : official journal of the International Association for the Study of the Liver · 2010Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, synthesis and secretion of connective tissue growth factor (CTGF)/CYR61/CTGF/NOV-family member 2 (CCN2) in cultures of hepatocytes were shown, which are sensitively up-regulated by exogenous TGF-beta. In this study TGF-beta-dependent CTGF/CCN2 expression in hepatocytes cultured under completely TGF-beta-free conditions was analysed by Western-blots, metabolic labelling, and CTGF-reporter gene assays. In alkaline phosphatase monoclonal anti-alkaline phosphatase complex (APAAP)-staining of cultured hepatocytes it was demonstrated that latent TGF-beta within the hepatocytes becomes rapidly detectable during culture indicating an intracellular demasking of the mature TGF-beta antigen. Subsequent signaling to theCTGF/CCN2 promoter occurs via p-Smad2, whereas p-Smad3 does not seem to be involved. Cycloheximide did not abolish the rapid immunocytochemical appearance of mature TGF-beta, but calpain inhibitors partially suppressed intracellular TGF-beta activation and subsequently CTGF up-regulation. Calpain treatment had the reverse effect. None of the inhibitors of extracellular TGF-beta signalling was effective in the reduction of spontaneous CTGF synthesis, but intracellularly acting Alk 4-/Alk 5-specific inhibitor SB-431542 was able to diminish CTGF expression. The assumption that latent intracellular TGF-beta is activated by calpains during culture-induced stress or injurious conditions in the liver in vivo was further validated by a direct effect of calpains on the activation of recombinant latent TGF-beta. In conclusion, these data are the first to suggest the possibility of intracrine TGF-beta signalling due to calpain-dependent intracellular proteolytic activation leading to transcriptional activation of CTGF/CCN2 as a TGF-beta-sensitive reporter gene. This mechanism might be deleterious for keeping long-term hepatocyte cultures due to TGF-beta-induced apoptosis and, further, might be of relevance for induction of apoptosis or epithelial-mesenchymal transition of hepatocytes in injured liver.
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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.