Autophagy: A new therapeutic target for liver fibrosis

Abstract

Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix (ECM) accumulation and degradation. The relentless production and progressive accumulation of ECM can lead to end-stage liver disease. Although significant progress has been achieved in elucidating the mechanisms of fibrogenesis, effective anti-fibrotic strategies are still lacking. Autophagy is an intracellular process of self-digestion of defective organelles to provide material recycling or energy for cell survival. Autophagy has been implicated in the pathophysiology of many human disorders including hepatic fibrosis. However, the exact relationships between autophagy and hepatic fibrosis are not totally clear and need further investigations. A new therapeutic target for liver fibrosis could be developed with a better understanding of autophagy.

Keywords: Autophagy; Liver fibrosis; Hepatic stellate cells; Antifibrotic target

Core tip: Autophagy plays dual roles in hepatic fibrosis. On the one hand, it attenuates fibrosis by reducing hepatic injury via inhibiting inflammatory reaction and maintaining cellular homeostasis. On the other hand, it fuels activation of hepatic stellate cells (HSCs) by lipophagy and induces type I collagen synthesis. More studies using Atg selective knockdown mice or primary HSCs derived from Atg-deleted mice are needed. Selective inhibition of autophagy in HSCs is an attractive antifibrotic strategy.