Rapamycin inhibits peritoneal fibrosis by modifying lipid homeostasis in the peritoneum.

Rapamycin inhibits peritoneal fibrosis by modifying lipid homeostasis in the peritoneum. Am J Transl Res. 2019;11(3):1473-1485 Authors: Liu J, Jiang CM, Feng Y, Zhu W, Jin B, Xia YY, Zhang QY, Xu PF, Zhang M Abstract Peritoneal fibrosis (PF) is characterized by progressive accumulation of extracellular matrix (ECM) components in the peritoneum under high glucose conditions. Rapamycin has previously been shown to inhibit ECM accumulation of peritoneal mesothelial cells (PMCs) and prevent PF. Here we explored the undefined mechanisms by which rapamycin inhibits ECM accumulation of PMCs. We used high-glucose peritoneal dialysis solution (PDS) in a mouse peritoneal dialysis model to induce in vivo PF and in human PMCs in vitro to stimulate ECM accumulation. The mice that received chronic PDS infusions showed typical features of PF, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expressions of α-smooth muscle actin and collagen I. Rapamycin significantly ameliorated these pathological changes. There was a parallel decrease in lipid accumulation in the peritoneum of rapamycin-treated mice. Rapamycin significantly inhibited high-glucose PDS-induced ECM accumulation and reduced the lipid droplet in human PMCs in the presence of PDS. The effects of rapamycin on intracellular lipid metabolism correlated with a series of steps in lipid homeostasis; namely, a decreas...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research