title: Effects of angiotensin receptor blocker on phenotypic alterations of podocytes in early diabetic nephropathy.
abstract: BACKGROUND
  Emerging evidence suggests that podocyte injury is a crucial event in the stage of diabetic nephropathy (DN), a process in which angiotensin II is implicated. In this study, the authors investigated the influence of irbesartan, an angiotensin receptor blocker, on the phenotypic alterations of podocytes in experimental DN.
  
  
  METHODS
  DN was induced by combination of high-sucrose, high-fat diet and intraperitoneal injection of low dose of streptozotocin (35 mg/kg) in spontaneously hypertensive rats. Diabetic rats were treated with irbesartan (50 mg/kg/d) by gavage for 8 weeks. Nondiabetic normotensive Wistar-Kyoto rats, which have the same genetic background as spontaneously hypertensive rat, were used as controls. The renal histological changes were investigated by light and electron microscopy. The epithelial marker of nephrin and mesenchymal marker of desmin were detected by real-time reverse transcriptase-polymerase chain reaction and Western blotting.
  
  
  RESULTS
  Compared with controls, diabetic rats were associated with mesangial matrix deposition, thickening of glomerular basement membrane, albuminuria, loss of podocytes and effacement of foot processes. Furthermore, the expression of nephrin was significantly reduced whereas desmin was increased. Irbesartan treatment not only lowered blood pressure and albuminuria but also attenuated podocyte loss, maintenance of nephrin expression and inhibition of desmin expression.
  
  
  CONCLUSIONS
  This study demonstrates that early irbesartan intervention attenuates the podocyte damage and ameliorates phenotypic alterations of podocytes, which provides a novel insight for the early application of angiotensin receptor blocker to prevent the development of DN.
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University, NanJing, China.
authors.forename: Hou-Yong
authors.initials: HY
authors.lastname: Dai
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Ri-Ning
authors.initials: RN
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003893:Desmin / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007150:Immunohistochemistry; D000077405:Irbesartan; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D001713:Biphenyl Compounds; D003893:Desmin; D008565:Membrane Proteins; D013777:Tetrazoles; C113267:nephrin; D000077405:Irbesartan