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Abstract: SA-PO696

Activation of mTORC1 Disrupted LDL Receptor Pathway: A Potential New Mechanism for the Progression of Peritoneal Fibrosis by High-Glucose PDS

Session Information

  • Peritoneal Dialysis - II
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis


  • Jing, Liu, Institute of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China., Nanjing, China

High-glucose peritoneal dialysis solution (PDS) play important roles in the peritoneal fibrosis. Recent studies demonstrated that high glucose could promote the intracellular accumulation of cholesterol via low density lipoprotein receptor (LDLr) in peritoneal mesothelial cell (PMC), which induce the expression of extracellular matrix protein in PMC. This study aimed to explore the potential mechanisms of the dysregulation of LDLr under the stimulation of high-glucose PDS.


Human PMCs (HMrSV5) was stimulated by high-glucose PDS. Oil red O and filipin staining were used to examine lipid accumulation. The expression of LDLr regulation, mammalian target of rapamycin complex1 (mTORC1) pathway and extracellular matrix proteins were assessed by real-time PCR and western blot.


Results demonstrated that high-glucose PDS increased lipid accumulation in PMCs. These effects were correlated with an increase in LDLr transcription, which was mediated through the up-regulation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), SREBP-2, and through enhanced translocation of the SCAP/SREBP-2 complex from endoplasmic reticulum (ER) to Golgi. In addition, our data indicated that there was a parallel increase in the expression of extracellular matrix proteins such as fibroblast specific protein-1, a-smooth muscle actin and collagen I. Further analysis showed that high-glucose PDS enhanced the protein phosphorylation of mTOR, eukaryotic initiation factor 4E-binding protein 1, and p70 S6 kinase. Interestingly, blocking mTORC1 activity inhibited the gene transcription of LDLr and decreased extracellular matrix deposition.


Our findings demonstrated that increased mTORC1 activity exacerbated peritoneal fibrosis by disrupting LDLr transcriptional regulation.


  • Government Support - Non-U.S.