Elevated expression of transforming growth factor β3 in carbon tetrachloride-treated rat liver and involvement of retinoid signaling

Abstract

Abstract. Transforming growth factor (TGF) β is a pro-fibrotic cytokine. While three isoforms (TGF-β1, 2 and 3) are known, the functional differences between them are obscure. To investigate the roles of TGF-β isoforms during liver fibrogenesis, male Wistar rats were administrated carbon tetrachloride (CCl 4 ) subcutaneously twice a week for two months. Livers were excised and sectioned for histochemical examinations. These livers were also used to quantitate the expression of genes associated with fibrogenesis, including TGF-β isoforms, as well as those associated with retinoid metabolism. Expression levels of Tgfb1 and Tgfb3 were up-regulated in CCl 4 -treated rat livers while that of Tgfb2 was not changed. The mRNAs for lecithin-retinol acyltransferase (Lrat) and retinoic acid hydroxylase, Cyp26a1, were also elevated. By immunohistochemical staining, TGF-β3 protein was found to be localized mainly in liver parenchymal cells (hepatocytes). These results indicate that retinoid mobilization likely takes place within the rat's liver following CCl 4 treatment, and suggest the possibility that the expression of Tgfb mRNA is regulated by retinoic acid receptors. Reporter analyses of a region of the Tgfb3 gene were performed using the rat liver parenchymal cell line, RLC-16, and a positively responsive region was identified within its intron.

Eggshell membrane ameliorates hepatic fibrogenesis in human C3A cells and rats through changes in PPARγ-Endothelin 1 signaling

“…TGFβs remains inactive while being recruited within this complex; however, when the liver has been injured, several proteases (metalloproteases, elastase and plasmin) cleave LTBP from the complex, releasing TGFβ and LAP. In this process, LTBPs regulate the TGFβs activity by facilitating its secretion, localizing the latent TGFβs to specific sites in the ECM26. The down-regulation of Tgfβ3 , Ltbps and the other growth factor-related genes such as Pdgfr and Vegfd may be one of the crucial mechanisms of ESM protection against HSC activation and fibrogenesis.…”

Tgfb3 and Mmp13 regulated the initiation of liver fibrosis progression as dynamic network biomarkers

“…47 Up-regulation of Tgfb3 expression was found in cirrhotic livers of primary biliary cirrhosis patients 51 and in CCl4-treated rat livers. 52 Higher Tgfb3 level in patients without non-alcoholic fatty liver diseases (NAFLD) was associated with higher chance of future development of NAFLD. 53 In Con A-induced autoimmune liver-damaged mice, abnormal HSC activation was accompanied by imbalance of Tgfb1 and Tgfb3 expressions in the early stage, which can line immune and hepatic fibrosis processes, leading to further switching and progressing of liver fibrosis.…”

“…Both are important mediators of fibrogenesis within the course of chronic hepatic allograft rejection 50 and attributed a key role in the pathogenesis of glioblastoma 47 . Up‐regulation of Tgfb3 expression was found in cirrhotic livers of primary biliary cirrhosis patients 51 and in CCl4‐treated rat livers 52 . Higher Tgfb3 level in patients without non‐alcoholic fatty liver diseases (NAFLD) was associated with higher chance of future development of NAFLD 53 .…”

“…The results indicated that clinically reliable diagnosis before stage 3 and early intervention are important to achieve a complete fibrosis reversion.In this study, 153 DNB genes were obtained, of which 52 were DEGs. The GO and pathway analysis revealed that the52 differentially expressed DNBs are enriched in known important fibrosis-associated pathways, such as retinol metabolism, TGF-β signalling pathway, ECM-receptor interaction, focal adhesion, hepatic fibrosis/ HSC activation, HIF1α signalling, MMP inhibition, LXR/RXR activation and retinol biosynthesis. These pathways are known key signalling pathways involved in the initiation and maintenance of HSC activation and increased synthesis of ECM and decreased ECM degradation.…”

Associations Between TGFA/TGFB3/MSX1 Gene Polymorphisms and Congenital Non-Syndromic Hearing Impairment in a Chinese Population

“…TGF-β was revealed to be involved in proliferation, differentiation, motility, adhesion, and death of normal cells and it can act as a promoter of tumors, invasion, and metastasis due to its role in stimulating angiogenesis and epithelial to mesenchymal transformation [ 20 , 21 ]. TGF-β was also found to play a role in embryonic development and wound healing in many molecular pathways, including tissue repair [ 22 ].…”