Autophagy: A Multifaceted Partner in Liver Fibrosis
Figure 1
Impact of autophagy on the cellular effectors of liver fibrogenesis. (a) Autophagy drives hepatic stellate cell activation from a quiescent, lipid-rich to a myofibroblastic, fibrogenic phenotype. In response to chronic liver injury, quiescent hepatic stellate cells lose their retinyl ester-containing lipid droplets and acquire myofibroblastic features, associated with fibrogenic properties. Autophagy in hepatic stellate cells is stimulated by oxidative and endoplasmic reticulum stress and may serve to provide free fatty acids from retinyl esters, thereby supplying the energy required for initiating and perpetuating the fibrogenic phenotype. (b) Autophagy as a protective anti-inflammatory process with antifibrogenic properties. Hepatic macrophage autophagy stimulates an anti-inflammatory pathway, that reuses the production of IL1 alpha and IL1 beta, resulting in inhibition of liver fibrogenesis. In addition, inhibition of Th17 polarisation by IL1 alpha and beta may also contribute to the antifibrogenic effects of macrophagic autophagy. (c) Hepatoprotective properties of autophagy may contribute to inhibition of fibrogenesis. Autophagy is generally considered as a survival pathway for hepatocytes, therefore limiting oxidative stress profibrogenic pathways for hepatic stellate cells such as ER stress and mitochondrial damage.
