Diabetes and exposure to peritoneal dialysis solutions alter tight junction proteins and glucose transporters of rat peritoneal mesothelial cells

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• 作者：Yazmin Debray-Garcí ; a^a ; Elsa I. Sá ; nchez^a ; Rafael Rodrí ; guez-Muñ ; oz^a ; Miguel A. Venegas^b ; Josue Velazquez^a ; José ; L. Reyes^a ; ^{jreyes@fisio.cinvestav.mx" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Peritoneal dialysis ; Tight junctions ; Epithelial to mesenchymal transition ; Oxidative stress ; Transepithelial electrical resistance
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：161
• 期：Complete
• 页码：78-89
• 全文大小：3477 K

文摘

To evaluate alterations in tight junction (TJ) proteins and glucose transporters in rat peritoneal mesothelial cells (RPMC) from diabetic rats and after treatment with peritoneal dialysis solutions (PDS) in vitro.

Methods

Diabetes was induced in female Wistar rats by streptozotocin (STZ)-injection. Twenty-one days after STZ-injection, peritoneal thickness and mesothelial cell morphology were studied by light microscopy and microvilli length and density by atomic force microscopy. RPMC were obtained from healthy and diabetic rats. Mesothelial phenotype, evaluated by cytokeratin and pan-cadherin, epithelial to mesenchymal transition (EMT), evaluated by alpha-smooth muscle action (α-SMA) and vimentin, TJ proteins, claudins-1 and -2, and occludin, and glucose transporters, sodium and glucose co-transporters (SGLT) -1 and -2 and facilitative glucose transporters (GLUT) -1 and -2 were analyzed. Also, transepithelial electrical resistance (TER) was measured. Oxidative stress was estimated by measuring reactive oxygen species production, and protein carbonylation, receptor for advanced glycation end products (RAGE), nuclear factor erythroid related factor-2 (Nrf-2), and expression of antioxidant enzymes.

Key findings

Peritoneal damage was present 21 days after STZ-injection. Diabetes induced changes in TJ and glucose transporters in RPMC together with decreased TER. RPMC from diabetic rats showed oxidative stress, which was enhanced by exposure to PDS. In addition, RPMC from diabetic rats showed early EMT.

Significance

To our knowledge, this is the first study that shows changes in TJ proteins and glucose transporters of RPMC from diabetic rats. All these alterations might explain the increased peritoneal permeability observed in diabetic patients undergoing peritoneal dialysis.