title: DNA microarray analysis of the epithelial-mesenchymal transition of mesothelial cells in a rat model of peritoneal dialysis.
abstract: 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.affiliation: Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Imai
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirahara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Morishita
authors.forename: Akir
authors.initials: A
authors.lastname: Onishi
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Muto
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011765:Pyruvaldehyde / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D011765:Pyruvaldehyde