title: Effect and mechanism of the Ang-(1-7) on human mesangial cells injury induced by low density lipoprotein.
abstract: Hyperlipidemia is an independent risk factor for renal disease, and lipid deposition is associated with glomerulosclerosis. The angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis (ACE2-Ang-(1-7)-Mas axis) has been reported to participate in lipid metabolic regulation but its mechanism remains unclear. We hypothesized Ang-(1-7) would reduce lipid uptake in human mesangial cells (HMCs) by regulating the low density lipoprotein receptor-sterol regulatory element binding proteins 2-SREBP cleavage activating protein (LDLr-SREBP2-SCAP) negative feedback system, and improve glomerulosclerosis by regulating the transforming growth factor-β1 (TGF-β1). In this study we found that ACE2 was undetected in HMCs. The administration of LDL caused normal LDLr-SREBPs-SCAP negative feedback effect. Exogenous Ang-(1-7) enhanced this negative feedback effect via down-regulating LDLr, SREBP2, and SCAP expression, and effectively inhibited LDL-induced lipid deposition and cholesterol increases. This enhanced inhibitory effect was reversed by the Mas receptor antagonist A-779. Meanwhile, Ang-(1-7) significantly decreased the high LDL-induced production of TGF-β1, an effect blocked by A-779. Interestingly, HMCs treated with Ang-(1-7) alone activated the TGF-β1 expression. Our results suggested that Ang-(1-7) inhibits LDL accumulation and decreases cholesterol levels via modulating the LDLr-SREBPs-SCAP negative feedback system through the Mas receptor. Moreover, Ang-(1-7) exhibits a dual regulatory effect on TGF-β1 in HMCs.
authors: Department of Nephrology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors: Wenhan
authors: W
authors: Huang
authors: Department of Nephrology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: hopetang@163.com.
authors: Lin
authors: L
authors: Tang
authors: Department of Nephrology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors: Ying
authors: Y
authors: Cai
authors: Department of Nephrology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors: Yaning
authors: Y
authors: Zheng
authors: Department of Nephrology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors: Ling
authors: L
authors: Zhang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D001391:Azo Compounds; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004396:Coloring Agents; D025461:Feedback, Physiological; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D004396:Coloring Agents; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011973:Receptors, LDL; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051782:Sterol Regulatory Element Binding Protein 2; D053773:Transforming Growth Factor beta1; D000803:Angiotensin I; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C011049:oil red O; C118790:angiotensin I (1-7)
keywords: Ang-(1-7); HMCs; LDL; Lipid induced renal injury