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DNA microarray analysis of the epithelial-mesenchymal transition of mesothelial cells in a rat model of peritoneal dialysis.
MedLine Citation:
PMID:  22073821     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Long-term peritoneal dialysis induces peritoneal hyperpermeability, and the subsequent loss of ultra-filtration causes patients to discontinue peritoneal dialysis. Glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are probably one of the primary causes for peritoneal injury. In the present study, we used a transcriptome analysis to determine the mechanism of peritoneal injury by GDPs. Rats were administered 20 mmol/L methylglyoxal (MGO) in PDF or 20 mmol/L formaldehyde in PDF (100 mL/kg) intraperitoneally for 21 days. The peritoneal membrane in rats that received MGO showed increased thickness and fibrosis. Mesenchymal-like cells over-proliferated on the surface of the peritoneum. A DNA microarray analysis revealed that the expression of 168 genes had increased by more than a factor of 4. The upregulated genes included those that code for extracellular matrix components (such as types III and lV collagen, among others), cell division cycle 42 (Cdc42), an enabled/vasodilator-stimulated phosphoprotein-like protein [Ena/VASP (Evl)], and actin-related protein 2/3 complex subunits (Arp2/3). In conclusion, a rat model of peritoneal injury by GDPs induced mesothelial cells to redifferentiate and proliferate, with upregulation of Cdc42, the Evl Ena/VASP, and Arp2/3, suggesting that GDPs induce fibrous thickening of the peritoneal membrane by redifferentiation of mesothelial cells, resulting in hyperpermeability of the peritoneum.
Authors:
Toshimi Imai; Ichiro Hirahara; Yoshiyuki Morishita; Akir Onishi; Makoto Inoue; Shigeaki Muto; Eiji Kusano
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Advances in peritoneal dialysis. Conference on Peritoneal Dialysis     Volume:  27     ISSN:  1197-8554     ISO Abbreviation:  Adv Perit Dial     Publication Date:  2011  
Date Detail:
Created Date:  2011-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104803     Medline TA:  Adv Perit Dial     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  11-5     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
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