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Angiotensin II mediates high glucose-induced TGF-beta 1 and fibronectin upregulation in HPMC through reactive oxygen species
- Angiotensin II mediates high glucose-induced TGF-beta 1 and fibronectin upregulation in HPMC through reactive oxygen species
- Noh, H; Ha, H; Yu, MR; Kim, YO; Kim, JH; Lee, HB
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- PERITONEAL DIALYSIS INTERNATIONAL
- vol. 25, no. 1, pp. 38 - 47
- high glucose; fibronectin; peritoneal fibrosis; reactive oxygen species; renin-angiotensin system; TGF-beta 1
- MULTIMED INC
- SCI; SCIE; SCOPUS
- Objective: To demonstrate the presence of an independent renin-angiotensin system (RAS) in the peritoneum and to determine the role of locally produced angiotensin (Ang) II in high gLucose-induced upregulation of transforming growth factor (TGF)-beta 1 and fibronectin by human peritoneal mesothelial cells (HPMC). Methods: In cultured HPMC, the expression of mRNAs for angiotensinogen, angiotensin-converting enzyme (ACE), Ang II type 1 receptor (AT1), and TGF-beta 1 was evaluated by real-time polymerase chain reaction; ACE, AT1, and fibronectin proteins by Western blot analysis; and Ang 1, Ang II, and TGF-beta 1 proteins by ELISA. Dichlorofluorscein (DCF)-sensitive cellular reactive oxygen species (ROS) were measured by fluorometry. Results: HPMC constitutively expressed all the components of RAS, and 50 mmoL/L D-glucose (high glucose) significantly increased angiotensinogen, ACE, and AT1 m RNAs and ACE, AT1, and Ang II proteins. Ang 11 increased TGF-beta 1 and fibronectin protein expression and DCF-sensitive cellular ROS. Losartan prevented Ang II-induced increase in cellular ROS. Both Losartan and captopril inhibited high gLucose-induced upregulation of TGF-beta 1 and fibronectin expression in HPMC in a dose-dependent manner. Antioxidant catalase and NADPH oxidase inhibitor diphenyleneiodinium effectively inhibited Ang 11-induced TGF-beta 1 and fibronectin protein expression. Conclusions: The present data demonstrate that HPMC constitutively express RAS, that Ang II produced by HPMC mediates high gLucose-induced upregulation of TGF-beta 1 and fibronectin expression, and that Ang II-induced TGF-beta 1 and fibronectin expression in HPMC is mediated by NADPH oxidase-dependent ROS. These data suggest that Locally produced Ang II and ROS in the peritoneum may be potential therapeutic targets in peritoneal fibrosis during long-term peritoneal dialysis.
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