Dimethylaminomicheliolide ameliorates peritoneal fibrosis through the activation of autophagy

This study aimed to investigate the protective effect of DMAMCL against PD-related PF and the mechanisms involved. In this study, we found that DMAMCL significantly decreased PD-induced extracellular matrix (ECM) deposition in a mouse model of PD, and that delayed DMAMCL administration halted the progression of PF in an established PD model. In addition, rapamycin administration induced autophagy and significantly ameliorated PF. The protective effect of DMAMCL against PF was weakened when co-administered with DMAMCL and 3-methyladenine. Inducing autophagy by rapamycin decreased transforming growth factor- β1–induced ECM accumulation in vitro. MCL promoted autophagy and inhibited ECM deposition. The anti-fibrotic effect of MCL was eliminated when knocking down ATG7 by siRNA. Taken together, DMAMCL might prevent against PF through activating autophagy. The anti-fibrotic effect of DMAMCL may be a new candidate for the treatment in patients with PD-related PF.Key messagesDimethylaminomicheliolide, the pro-drug of micheliolide, protects against peritoneal fibrosis in a mouse peritoneal dialysis model.Micheliolide inhibits TGF- β1-induced extracellular matrix accumulation in vitro.Autophagy plays a protective role against peritoneal fibrosis.The antifibrogenic effect of dimethylaminomicheliolide may be due to the activation of autophagy.
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research