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Abstract: SA-PO710

Metformin Ameliorates the Phenotype Transition of Peritoneal Mesothelial Cells and Peritoneal Fibrosis via a Modulation of Oxidative Stress

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


  • Kang, Duk-Hee, Ewha University College of Medicine, Seoul, Korea (the Republic of)
  • Kang, Hyun-Jung, Ewha Womans University , Seoul, Korea (the Republic of)
  • Ryu, Eun sun, Ewha Womans University School of Medicine, Seoul, Korea (the Republic of)
  • Kim, Dal-ah, Ewha Womans University Medical Center, Seoul, seoul, Korea (the Republic of)

Phenotype transition of peritoneum is an early mechanism of peritoneal fibrosis. Metformin, 5'-adenosine monophosphate-activated protein kinase (AMPK) activator, has recently received a new attention due to its preventive effect on organ fibrosis and cancer metastasis by inhibiting epithelial-to-mesenchymal transition (EMT)


EMT was evaluated by morphological changes of human peritoneal mesothelial cells (HPMCs) and the expressions of E-cadherin and α-SMA by real time PCR, WB and ICC. ROS generation was assessed by DCF-DA staining, NOX activity, NOX mRNA expressions, and MitoSoxR staining. Activation of Smad2/3, MAPK, GSK-3β phosphorylation, nuclear translocation of β-catenin and snail expression were assessed. The effect of AMPK gene silencing or AMPK inhibitor on peritoneal EMT was evaluated. Animal model of peritoneal dialysis was established by daily infusion of 4.25% glucose-based dialysate for 8 weeks via intraperitoneal catheter. Effects of metformin (50 mg/kg/day, ip) on EMT, peritoneal thickening and an expression of markers of oxidative stress were investigated.


TGFβ1 (1 ng/mL)-induced EMT in HPMC was ameliorated by metformin. Metformin (1 ng/mL) alleviated NOX - and mitochondria-mediated ROS production with an increase in superoxide dismutase (SOD) activity and SOD2 expression. Metformin inhibited the activation of Smad2/3 and MAPK, GSK-3β phosphorylation, nuclear translocalization of β-catenin and Snail. Effect of metformin on TGFβ1-induced EMT was ameliorated by either Compound C (20 μg/mL) or AMPK gene silencing. Another AMPK agonist, 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (10 μM) partially blocked TGF-β1-induced EMT. In animal model of PD, intraperitoneal metformin decreased the peritoneal thickness and EMT with an increase in ratio of reduced to oxidized glutathione and the expression of SOD whereas it decreased the expression of nitrotyrosine and 8-hydroxy-2’-deoxyguanosine


A modulation of AMPK in peritoneum can be a novel tool to prevent peritoneal fibrosis by providing a favorable oxidant/anti-oxidant milieu in peritoneal cavity and ameliorating phenotype transition of peritoneal mesothelial cells