Small interfering RNA targeting ILK inhibits EMT in human peritoneal mesothelial cells through phosphorylation of GSK-3β

Lingrong Luo, Hong Liu, Zheng Dong, Lin Sun, Youming Peng, Fuyou Liu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Emerging evidence has suggested that human peritoneal mesothelial cells (HPMCs) undergo epithelial-mesenchymal transition (EMT) in peritoneal fibrosis. The molecular mechanisms underlying peritoneal fibrosis and the key molecules involved are not yet fully elucidated. In order to enhance the understanding of peritoneal fibrosis, the present study investigated the roles of integrin-linked kinase (ILK) and glycogen synthase kinase 3β (GSK-3β) in high glucose-induced phenotypic alterations of HPMCs. It was observed that HPMCs exhibited a cobblestone morphology under normal glucose conditions, whereas under high glucose conditions they had a spindle morphology. Additionally, under high glucose conditions it was found that E-cadherin expression was decreased and vimentin expression was increased in HPMCs, suggesting HPMCs underwent EMT. ILK expression in high glucose conditions was also increased in a dose- and time-dependent manner. The role of ILK in the induction of EMT in HPMCs was further investigated using small interfering RNA (siRNA). Following knockdown of ILK gene expression by siRNA, low vimentin expression as well as high E-cadherin expression were observed, suggesting that EMT was inhibited. ILK-knockdown also inhibited phosphorylation of GSK-3β. These results indicate that ILK-knockdown inhibits EMT of HPMCs through inhibition of GSK-3β phosphorylation. These findings suggest that ILK may be used as a novel diagnostic and therapeutic target for HPMC fibrosis in the future.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalMolecular Medicine Reports
Volume10
Issue number1
DOIs
Publication statusPublished - Jul 2014

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Keywords

  • Epithelial-mesenchymal transition
  • Glycogen synthase kinase 3β
  • Human peritoneal mesothelial cells
  • Integrin-linked kinase
  • Peritoneal dialysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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