title: High glucose induces activation of the local renin‑angiotensin system in glomerular endothelial cells.
abstract: Activation of the intrarenal renin‑angiotensin system (RAS), which has been identified in podocytes and mesangial cells, is a novel mechanism in the progression of diabetic kidney disease (DKD). The present study aimed to identify the local RAS in glomerular endothelial cells (GEnCs). Rat GEnCs were stimulated by culture medium containing 30 mmol/l glucose for 12, 24, 48 and 72 h. Angiotensin II (Ang II) concentrations in cell lysates and culture media were examined by ELISA and mRNA levels of angiotensinogen and renin in cell lysates were analyzed by quantitative polymerase chain reaction. Ang II type 1 receptor (AT1R), Ang II type 2 receptor (AT2R), renin and angiotensinogen levels in cell lysates were determined by western blot analysis. Localization of intracellular AT1R, AT2R, angiotensinogen and renin was identified by confocal immunofluorescence microscopy. Consequently, high glucose (HG) increased intracellular and extracellular Ang II levels. Captopril and chymostatin (inhibitor of chymase, an enzyme that converts Ang I to Ang II) were able to antagonize HG‑induced Ang II generation. Moreover, HG increased angiotensinogen production in GEnCs and reduced renin mRNA expression without altering renin protein production. However, HG decreased AT1R levels and resulted in AT2R shifting from the nuclear to perinuclear region in GEnCs. In conclusion, HG activated the intracellular RAS in rat GEnCs and the underlying mechanism may involve angiotensin‑converting enzyme (ACE) and non‑ACE pathways. The effects of HG on GEnCs may also involve the substrate and receptors of Ang II.
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Hui
authors: H
authors: Peng
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors: Yan-Fang
authors: YF
authors: Xing
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Zeng-Chun
authors: ZC
authors: Ye
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Can-Ming
authors: CM
authors: Li
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Peng-Li
authors: PL
authors: Luo
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Ming
authors: M
authors: Li
authors: Department of Internal Medicine, Division of Nephrology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors: Tan-Qi
authors: TQ
authors: Lou
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis; D000808:Angiotensinogen / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis; D012083:Renin / Q000096:biosynthesis* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin; D005947:Glucose