Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat.
Qi Z, Atsuchi N, Ooshima A, Takeshita A, Ueno H.
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka 812-8582, Japan.
We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCATbeta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis. In rats that received a single application of AdCATbeta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated. All AdCATbeta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCATbeta-TR-untreated rats died of liver dysfunction. The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearly in a persistent fibrosis model that prevention of fibrosis by anti-TGF-beta intervention could be therapeutically useful.
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PMID: 10051644 [PubMed - indexed for MEDLINE]PMCID: PMC26786