Hepatic stellate cell activation and survival (HSC activation)

Hepatic stellate cell (HSC) activation and survival is a pivotal cellular process in the development of liver fibrosis and cirrhosis (Friedman SL, Physiol Rev, 2008). In the healthy liver, HSCs are quiescent cells that store vitamin A; however, in response to chronic injury, they undergo activation, transforming into proliferative, contractile myofibroblasts that secrete excessive extracellular matrix (ECM) proteins (Tsuchida T & Friedman SL, Nat Rev Gastroenterol Hepatol, 2017). The survival of these activated cells is a key factor in the persistence of fibrosis, as they become resistant to apoptosis through the upregulation of pro-survival pathways such as TGF-beta, PDGF, and Bcl-2 (Puche JE, et al., Compr Physiol, 2013). While 'HSC activation' is not a single molecular target, it represents a critical therapeutic focal point where various drugs aim to inhibit specific receptors or enzymes to halt or reverse fibrotic progression. Current pharmacological strategies focus on inducing HSC senescence, reversion to quiescence, or selective clearance through apoptosis to treat conditions like metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis.

Other names

HSC activationHepatic stellate cell myofibroblastic transformationHSC survival signalingStellate cell activation

Inhibition of the transdifferentiation of quiescent hepatic stellate cells into myofibroblasts and the promotion of activated cell clearance via apoptosis or reversion.