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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Angiotensin II, Cell Culture Techniques, Dialysis Solutions, Dose-Response Relationship, Drug, Epithelial Cells, Fibronectins, Glucose, Humans, Peritoneum, RNA, Messenger, Reactive Oxygen Species, Transforming Growth Factor beta, Transforming Growth Factor beta1, Up-Regulation.
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Does angiotensin II mediate high glucose-induced TGF-beta1 and fibronectin upregulation in HPMC through reactive oxygen species? Context: 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)-beta1 and fibronectin by human peritoneal mesothelial cells (HPMC). In cultured HPMC, the expression of mRNAs for angiotensinogen, angiotensin-converting enzyme (ACE), Ang II type 1 receptor (AT1), and TGF-beta1 was evaluated by real-time polymerase chain reaction; ACE, AT1, and fibronectin proteins by Western blot analysis; and Ang I, Ang II, and TGF-beta1 proteins by ELISA. Dichlorofluorescein (DCF)-sensitive cellular reactive oxygen species (ROS) were measured by fluorometry. HPMC constitutively expressed all the components of RAS, and 50 mmol/L D-glucose (high glucose) significantly increased angiotensinogen, ACE, and AT1 mRNAs and ACE, AT1, and Ang II proteins. Ang II increased TGF-beta1 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-beta1 and fibronectin expression in HPMC in a dose-dependent manner. Antioxidant catalase and NADPH oxidase inhibitor diphenyleneiodinium effectively inhibited Ang II-induced TGF-beta1 and fibronectin protein expression.
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The present data demonstrate that HPMC constitutively express RAS, that Ang II produced by HPMC mediates high glucose-induced upregulation of TGF-beta1 and fibronectin expression, and that Ang II-induced TGF-beta1 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. Final Decision: yes