[Phosphorylation of glycogen synthase kinase-3beta induces epithelial mesenchymal transition in human peritoneal mesothelial cells]

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Apr;35(4):329-34. doi: 10.3969/j.issn.1672-7347.2010.04.008.
[Article in Chinese]

Abstract

Objective: To investigate the role of phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) inducing epithelial mesenchymal transition in human peritoneal mesothelial cells (HPMC).

Methods: Primary HPMC was harvested from human omental tissue and maintained under defined in vitro conditions. The expression of p-GSK-3beta and total GSK-3beta in HMPC was detected by Western blot after incubation with different concentrations (0, 5, 10, 20, and 40 mmol/L)of LiCl at different time points (0, 1, 3, 6, and 12 h). The protein expression of E-cadherin and alpha-SMA was also examined after treatment with 20 mmol/L LiCl according to different time courses. The intracellular distribution and expression of alpha-SMA were determined by indirect immunofluorescence.

Results: LiCl stimulated phosphorylation of GSK-3beta and the effect was time-dependent and concentration-dependent to limited extent (P<0.05). The expression of alpha-SMA increased (P<0.05) and the expression of E-cadherin decreased significantly (P<0.05) after 24 h stimulation by 20 mmol/L LiCl. The indirect immunoflurescence showed that the expression of alpha-SMA in HPMC increased significantly after 24 h incubation with 20 mmol/L LiCl.

Conclusion: The phosphorylation of GSK-3beta leads HMPC to epithelial mesenchymal transition and provides new clue for the treatment of peritoneal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cadherins / metabolism
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Lithium Chloride / pharmacology
  • Mesoderm / cytology*
  • Mesoderm / drug effects
  • Peritoneum / cytology
  • Phosphorylation

Substances

  • ACTA2 protein, human
  • Actins
  • Cadherins
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Lithium Chloride