TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis: Updated

TLDR: The present review builds on knowledge of the last two decades about TGF-β function in myofibroblast generation and fibrogenesis, and presents the milestone discoveries from the recent 3–5 years, which include findings on downstream targets with fibrogenic function, pathways that facilitate T GF-β expression in HSC, and miRNAs regulated by or regulating the TDF-β pathway.

Abstract: TGF-β is a pro-fibrogenic and antiproliferative protein with multiple functions depending on the cellular context. In liver fibrosis, TGF-β was identified as very robust driver of hepatic stellate cell (HSC) activation and extracellular matrix production, and a plethora of approaches targeting the TGF-β signaling pathway were successfully used to tackle fibrogenesis in animal models of chronic liver diseases. The present review builds on knowledge of the last two decades about TGF-β function in myofibroblast generation and fibrogenesis, and presents the milestone discoveries from the recent 3–5 years. These include findings on downstream targets with fibrogenic function, pathways that facilitate TGF-β expression in HSC, and miRNAs regulated by or regulating the TGF-β pathway. Further, recent data on TGF-β signaling, its integration with other pathways, and TGF-β signaling regulators identified in the setting of fibrotic liver disease are provided. Additionally, we will discuss TGF-β and epithelial-to-mesenchymal transition in liver fibrosis, and what we have learned from other fibrotic diseases, besides liver. Finally, challenges and opportunities for TGF-β-directed therapies in HSC activation, liver fibrosis, and disease progression are discussed.