TGF-β in progression of liver disease

Abstract

Transforming growth factor-β (TGF-β) is a central regulator in chronic liver disease contributing to all stages of disease progression from initial liver injury through inflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Liver-damage-induced levels of active TGF-β enhance hepatocyte destruction and mediate hepatic stellate cell and fibroblast activation resulting in a wound-healing response, including myofibroblast generation and extracellular matrix deposition. Being recognised as a major profibrogenic cytokine, the targeting of the TGF-β signalling pathway has been explored with respect to the inhibition of liver disease progression. Whereas interference with TGF-β signalling in various short-term animal models has provided promising results, liver disease progression in humans is a process of decades with different phases in which TGF-β or its targeting might have both beneficial and adverse outcomes. Based on recent literature, we summarise the cell-type-directed double-edged role of TGF-β in various liver disease stages. We emphasise that, in order to achieve therapeutic effects, we need to target TGF-β signalling in the right cell type at the right time.

Effects of FGF21‐secreting adipose‐derived stem cells in thioacetamide‐induced hepatic fibrosis

“…TGF‐β activates HSCs and promotes liver fibrosis progression 12. Collagen, TIMP‐1 and α‐SMA are TGF‐β target genes, and are expressed via the JNK and Smad2/3 signalling pathway 13. Our results showed that ADSCs transplantation reduced TAA‐induced JNK and Smad2/3 activation in vivo, with more potent inhibition by transplantation of FGF21_ADSCs than Empty_ADSCs.…”

Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

“…TGF-β1, one of the TGF-β isoforms, is the most potent profibrogenic factor. TGF-β signaling promotes fibroblast differentiation into α-smooth muscle actin (α-SMA) expressing myofibroblasts and stimulates collagen deposition after a variety of injuries in tissues, including, among others, the liver (5)(6)(7)(8) and the skin (9). Furthermore, myofibroblastlike cells respond to TGF-β by expressing increased amounts of this factor, thus contributing to fibrosis development through autocrine and paracrine loops of TGF-β-stimulated collagen production (10).…”

Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection

“…To note, the TGF-b is not produced exclusively by the Treg cells, in fact, within inflammatory microenvironment, it is secreted by Kupffer cells and activated hepatic stellate cells, indicating that its reduction not necessarily to reflect the frequency of Treg cells, but rather the improving the hepatic condition [46]. Moreover, CHC patients at the completion of the dietary regimen showed the same trend for the serum levels of HA.…”