title: Inhibition of integrin-linked kinase by angiotensin II receptor antagonist, irbesartan attenuates podocyte injury in diabetic rats.
abstract: BACKGROUND
  Integrin-linked kinase (ILK) dysregulation is involved in the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of angiotensin II receptor blocker (ARB), irbesartan, on ILK expression and podocyte injury in DN.
  
  
  METHODS
  DN was induced by the combined feeding of high-sucrose, high-fat diet and intra-peritoneal injection of low dose of streptozotocin (35 mg/kg) in spontaneously hypertensive rats. Diabetic rats were treated with irbesartan (50 mg×kg(-1)×d(-1)) by gavage for 8 weeks. The renal morphologic changes and podocyte injury were investigated by light and electron microscopy, and the ILK expression was evaluated by real-time RT-PCR and Western blotting analysis.
  
  
  RESULTS
  Diabetic rats exhibited with the similar clinical feature of type 2 DN. Morphologically, they were characterized by expansion of mesangial matrix, loss of podocyte and podocyte injury. Impressively, compared to controls, the ILK expression in diabetic rats were upregulated, which were positively correlated with both podocyte injury and albuminuria. Irbesartan significantly prevented ILK overexpression, along with the amelioration of podocyte injury and albuminuria.
  
  
  CONCLUSIONS
  ILK plays an important role in mediating podocyte injury in DN; irbesartan inhibits ILK upregulation and attenuates podocyte injury, which might offer a new insight into the role of ARB in preventing DN progression.
authors.affiliation: Department of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu 210009, 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: Kun-ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Bi-cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D050199:Podocytes / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000627:therapeutic use*; D000099200:Scaffold Protein ILK
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D000077405:Irbesartan; D017346:Protein Serine-Threonine Kinases; D013777:Tetrazoles; D000099200:Scaffold Protein ILK