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DOI: 10.1371/journal.pone.0108593
论文题名:
Serum Response Factor Accelerates the High Glucose-Induced Epithelial-to-Mesenchymal Transition (EMT) via Snail Signaling in Human Peritoneal Mesothelial Cells
作者: Lijie He; Weijuan Lou; Lihua Ji; Wei Liang; Meilan Zhou; Guoshang Xu; Lijuan Zhao; Chen Huang; Rong Li; Hanmin Wang; Xiangmei Chen; Shiren Sun
刊名: PLOS ONE
ISSN: 1932-6203
出版年: 2014
发表日期: 2014-10-10
卷: 9, 期:10
语种: 英语
英文关键词: Fibrosis ; Glucose ; Polymerase chain reaction ; Small interfering RNAs ; Effluent ; Electrophoretic mobility shift assay ; Plasmid construction ; Medical dialysis
英文摘要: 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.
URL: http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0108593&type=printable
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/19034
Appears in Collections:过去全球变化的重建
影响、适应和脆弱性
科学计划与规划
气候变化与战略
全球变化的国际研究计划
气候减缓与适应
气候变化事实与影响

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作者单位: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xingyuan Hospital, the Fourth Hospital of Yulin, Yulin, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, the Ninth Hospital of Xi'an, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing, China;Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China;State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan xi, China

Recommended Citation:
Lijie He,Weijuan Lou,Lihua Ji,et al. Serum Response Factor Accelerates the High Glucose-Induced Epithelial-to-Mesenchymal Transition (EMT) via Snail Signaling in Human Peritoneal Mesothelial Cells[J]. PLOS ONE,2014-01-01,9(10)
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