Mammalian Target of Rapamycin Complex 1 Activation Disrupts the Low-Density Lipoprotein Receptor Pathway: A Novel Mechanism for Extracellular Matrix Accumulation in Human Peritoneal Mesothelial Cells.

Mammalian Target of Rapamycin Complex 1 Activation Disrupts the Low-Density Lipoprotein Receptor Pathway: A Novel Mechanism for Extracellular Matrix Accumulation in Human Peritoneal Mesothelial Cells. Am J Nephrol. 2018 Nov 13;48(5):357-368 Authors: Liu J, Zhu W, Jiang CM, Feng Y, Xia YY, Zhang QY, Xu PF, Zhang M Abstract Peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation. Increasing evidence has suggested that ECM synthesis was increased in human peritoneal mesothelial cells (HPMCs) under high-glucose conditions, but the effects of high-glucose peritoneal dialysis solution (PDS) on ECM synthesis have not been fully elucidated. The aim of this study was to explore the potential mechanisms of high-glucose PDS-induced production of ECM in HPMCs. HPMCs were stimulated by high-glucose PDS. The activity of mammalian target of rapamycin complex 1 (mTORC1) was inhibited by rapamycin or regulatory-associated protein of mTOR (raptor) siRNA. Morphological changes in the cells were observed under an inverted microscope. Oil red O, filipin staining and high-performance liquid chromatography were used to examine lipid accumulation. The expression of low-density lipoprotein receptor (LDLr) regulation, the mTORC1 pathway and ECM-associated markers were assessed by real-time polymerase chain reaction and western blot analysis. The results showed that after treatment with PDS, HPMCs showed notable elong...
Source: American Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: Am J Nephrol Source Type: research