Serum response factor accelerates the high glucose-induced Epithelial-to-Mesenchymal Transition (EMT) via snail signaling in human peritoneal mesothelial cells.

Abstract

BACKGROUND:

Epithelial-to-Mesenchymal Transition (EMT) induced by glucose in human peritoneal mesothelial cells (HPMCs) is a major cause of peritoneal membrane (PM) fibrosis and dysfunction.

METHODS:

To investigate serum response factor (SRF) impacts on EMT-derived fibrosis in PM, we isolated HPMCs from the effluents of patients with end-stage renal disease (ESRD) to analyze alterations during peritoneal dialysis (PD) and observe the response of PM to SRF in a rat model.

RESULTS:

Our results demonstrated the activation and translocation of SRF into the nuclei of HPMCs under extensive periods of PD. Accordingly, HPMCs lost their epithelial morphology with a decrease in E-cadherin expression and an increase in α-smooth muscle actin (α-SMA) expression, implying a transition in phenotype. PD with 4.25% glucose solution significantly induced SRF up-regulation and increased peritoneal thickness. In immortal HPMCs, high glucose (HG, 60 mmol/L) stimulated SRF overexpression in transformed fibroblastic HPMCs. SRF-siRNA preserved HPMC morphology, while transfection of SRF plasmid into HPMCs caused the opposite effects. Evidence from electrophoretic mobility shift, chromatin immunoprecipitation and reporter assays further supported that SRF transcriptionally regulated Snail, a potent inducer of EMT, by directly binding to its promoter.

CONCLUSIONS:

Our data suggested that activation of SRF/Snail pathway might contribute to the progressive PM fibrosis during PD.

• Authors: Lijie He, Weijuan Lou, Lihua Ji, Wei Liang, Meilan Zhou, Guoshang Xu, Lijuan Zhao, Chen Huang, Rong Li, Hanmin Wang, Xiangmei Chen, Shiren Sun
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e108593 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25303231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serum Response Factor
• Glucose

Topics

• Animals
• Cells, Cultured
• Epithelial-Mesenchymal Transition
• Glucose (metabolism)
• Humans
• Kidney Failure, Chronic (complications, therapy)
• Male
• Peritoneal Dialysis
• Peritoneal Fibrosis (metabolism, pathology)
• Peritoneum (cytology, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Serum Response Factor (metabolism)
• Signal Transduction