Pituitary tumor transforming gene as a novel regulatory factor of liver fibrosis.

AIMS:Pituitary tumor-transforming gene is involved in multiple cellular pathways. We studied the development of liver fibrosis induced by thioacetamide (TAA) in knockout and wildtype mice. MAIN METHODS:Liver fibrosis in and mice was induced by escalating dose TAA treatment (50-400mg/kg, i.p.) for 12 weeks and assessed by histochemistry, immunohistochemistry, liver hydroxyproline, serum fibrosis markers and fibrosis-related mRNA expression by real-time PCR determination. KEY FINDINGS:Both duanyu1547G+/+ and duanyu1547G-/- mice treated with TAA developed signs of fibrosis and inflammatory cell infiltration. However, histological signs of bridging fibrosis and connective tissue square morphometry were significantly attenuated in mice lacking α-SMA immunohistochemistry revealed that hepatic stellate cell activation was markedly reduced in duanyu1547G-/- mice compared to wildtype controls. Hepatic hydroxyproline levels were significantly lower in fibrotic duanyu1547G-/- group. The serum TNFα and hepatic TNFα mRNA expression were significantly lower in fibrotic duanyu1547G-/- animals, as well as hepatic TGFβ and VEGF mRNA levels compared to TAA-treated wildtype controls. Serum hyaluronate and TGFβ levels were markedly elevated in fibrotic mice of both genotypes, but were not altered by the absence of fibrosis development is significantly ameliorated in duanyu1547G-/- mice. These animals demonstrated diminished stellate cell activation, suppressed circulating serum markers of inflammation, fibrogenesis and angiogenesis. The presented findings suggest that is functionally required for hepatic fibrosis progression in an animal model of chronic liver injury. duanyu1547G can be considered as a new important target for prevention and treatment of liver fibrosis/cirrhosis.

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