EMAIL THIS PAGE TO A FRIEND

Life sciences

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


PMID 25936962

Abstract

Pituitary tumor-transforming gene (PTTG) is involved in multiple cellular pathways. We studied the development of liver fibrosis induced by thioacetamide (TAA) in knockout (PTTG-/-) and wildtype (PTTG+/+) mice. Liver fibrosis in PTTG+/+ and PTTG-/- 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. Both PTTG+/+ and PTTG-/- 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 PTTG. α-SMA immunohistochemistry revealed that hepatic stellate cell activation was markedly reduced in PTTG-/- mice compared to wildtype controls. Hepatic hydroxyproline levels were significantly lower in fibrotic PTTG-/- group. The serum TNFα and hepatic TNFα mRNA expression were significantly lower in fibrotic PTTG-/- 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 PTTG. TAA-induced fibrosis development is significantly ameliorated in PTTG-/- mice. These animals demonstrated diminished stellate cell activation, suppressed circulating serum markers of inflammation, fibrogenesis and angiogenesis. The presented findings suggest that PTTG is functionally required for hepatic fibrosis progression in an animal model of chronic liver injury. PTTG can be considered as a new important target for prevention and treatment of liver fibrosis/cirrhosis.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

163678
Thioacetamide, ACS reagent, ≥99.0%
C2H5NS
172502
Thioacetamide, reagent grade, 98%
C2H5NS