Effect of fetuin, a TGFβ antagonist and pentoxifylline, a cytokine antagonist on hepatic stellate cell function and fibrotic parameters in fibrosis

Fetuin-A Pretransplant Serum Levels, Kidney Allograft Function and Rejection Episodes: A 3-Year Posttransplantation Follow-Up

“…Incubation of fetuin-A with hepatic stellate cells significantly inhibited collagen synthesis in hepatic stellate cells, potentially linking fetuin-A as an antifibrotic agent and cytokine antagonist [10,11] . IF/TA are well-recognized reasons for chronic allograft failure.…”

“…Fetuin-A binds to multiple ligands, including the fibrogenic growth factor TGF-␤ , thus acting as a soluble receptor-like antagonist of TGF-␤ actions [10] . It could be demonstrated that incubation of fetuin-A with hepatic stellate cells significantly inhibited collagen synthesis in hepatic stellate cells, potentially linking fetuin-A as an antifibrotic agent and cytokine antagonist [10,11] .…”

“…The effect of pretransplant fetuin-A serum levels on allograft outcome, rejection episodes and long-term follow-up has not been elucidated in a large patient cohort. Regarding the various features of fetuin-A in terms of being downregulated during inflammation [16] , inhibiting calcification and fibrosis [4,10,11] , it may be speculated that pretransplant fetuin-A serum levels predict allograft outcome and rejection episodes. Therefore we investigated the relationship between fetuin-A levels prior to kidney transplantation and outcome 3 years after transplantation in 206 patients.…”

Serum fetuin A/α2HS-glycoprotein levels in patients with non-alcoholic fatty liver disease: relation with liver fibrosis

“…These results suggest the existence of mechanisms by which increased AHSG can be directly associated with liver injury independently from insulin resistance. Verma-Gandhu et al 20 have previously reported that AHSG is a natural antagonist of TGF-beta -the key mediator of hepatic fibrosis -and that administration of this molecule may be beneficial in liver fibrosis through the inhibition of hepatic stellate cell function and collagen synthesis. These data therefore seem to suggest that levels of AHSG should be lower, not higher, in patients with more severe fibrosis.…”

Pancreatic and Hepatic Fibrosis: Remarkable Similarities

“…We were the first to reported on the role for platelet derived growth factor (PDGF) in experimental models of hepatic fibrosis [8,9] and we showed that PTX blocked fibrosis via an effect on PDGF and that this occurred by blocking phosphorylation of c-jun on serine 73 [10]. We began investigations of non alcoholic steatohepatitis (NASH) mediated fibrosis [11,12] and reported that ribavirin but not interferon inhibited fibrosis also associated with HCV and that this effect was mediated by the block of phosphorylation of c-jun on ser 73 and resulted in decreased synthesis of collagen and hepatic stellate cell (HSC) proliferation [13]. We reported that PTX decreased NASH sera-stimulated FSI (our patented diagnostic test for fibrosis using HSCs as the target cell) and c-Jun phosphorylation as assessed by 3 H-thymidine incorporation and Western analysis respectively, such that NASH patient sera stimulated HSC proliferation and increased phosphorylated c-Jun in HSCs and that PTX significantly decreased NASH patient sera stimulated HSC proliferation and decreased NASH sera-stimulated phosphorylated c-Jun in HSCs [14].…”