Autophagic degradation of MVBs in LSECs promotes Aldosterone induced-HSCs activation.

Aldo-induced Autophagic degradation of MVBs in LSECs promotes a decrease in the quantity and quality of EVs derived from LSECs, resulting in the activation of HSCs and liver fibrosis under hyperaldosteronism. Modulating the autophagy level of LSECs and their EV secretion may represent a promising therapeutic approach for treating liver fibrosis. In a physiological state, LSECs transmit inhibitory signals to HSCs via the secretion of EVs that are rich in miR-342-5p. However, in pathological conditions, the elevated levels of serum aldosterone induce capillarization and excessive autophagy in LSECs. This autophagy leads to the degradation of MVBs in LSECs, resulting in a reduction of the number of EVs and miR-342-5p content within EVs. This reduction ultimately leads to a diminished inhibitory signal transmitted to HSCs, thereby activating HSCs and promoting the development of liver fibrosis.