{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:57:25Z","timestamp":1778014645812,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,11,26]],"date-time":"2004-11-26T00:00:00Z","timestamp":1101427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p><jats:bold>Abstract: Background\/Aims: <\/jats:bold> Many studies have reported that hypoxia might be associated with angiogenesis and fibrogenesis, and the level of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) was increased in fibrotic liver and maximal at cirrhosis. Therefore, we examined the expression of TGF\u2010\u03b21, phosphorylated\u2010Smad2\/3 (p\u2010Smad2\/3) of the TGF\u2010\u03b2 immediate down stream signaling system and hypoxic status during hepatic fibrogenesis.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> Fibrosis of rats was induced by carbon tetrachloride. Collagens were detected with Azan stain. Immunohistochemistry and immunoblotting was used.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> TGF\u2010\u03b21 was mainly produced by hypoxic hepatocytes at cirrhosis although myofibroblasts (MFBs) and macrophages producing TGF\u2010\u03b21 were decreased. Moreover, distribution of p\u2010Smad2\/3 in hepatocytes was consistent with those of hypoxic hepatocytes regardless of MFBs. Furthermore, in recovery, most MFBs disappeared, whereas positive reactions of p\u2010Smad2\/3 still existed in the hepatocytes of hypoxic areas. Therefore, TGF\u2010\u03b21 expression in hepatocytes might have been associated with hypoxia.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> We put forward the hypothesis that TGF\u2010\u03b21 is mainly produced by MFBs and macrophages at early and middle stages of fibrotic processes, but it is predominantly released by hypoxic hepatocytes in the last fibrotic stage or cirrhosis.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2004.0961.x","type":"journal-article","created":{"date-parts":[[2004,11,26]],"date-time":"2004-11-26T13:36:39Z","timestamp":1101476199000},"page":"658-668","source":"Crossref","is-referenced-by-count":43,"title":["Hypoxia potentiates transforming growth factor\u2010\u03b2 expression of hepatocyte during the cirrhotic condition in rat 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