title: 1,25-Dihydroxyvitamin D3 ameliorates podocytopenia in rats with adriamycin-induced nephropathy.
abstract: OBJECTIVE
  To investigate the role of α3β1 integrin and α/β-dystroglycan in protective effects of 1,25(OH)2D3 on podocytes in rats with adriamycin-induced nephropathy.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into three groups: control group (NC), nephropathy group (NE), and nephropathy+1,25(OH)2D3 group (ND). Rats in NE and ND group were injected intravenously with adriamycin (0.1 mg/10 g body weight) to induce nephropathy, and those in ND group were then subcutaneously treated with 1,25(OH)2D3 for 8 weeks. Urinary protein level, number of urine podocytes, foot process width and glomerulosclerotic index were determined. Nephrin and podocin mRNA and protein expressions were determined by RT-PCR and western blot, respectively. Podocyte density and expressions of α3β1 integrin and α/β-dystroglycan (DG) were analyzed by immunohistochemistry and western blot, respectively.
  
  
  RESULTS
  The increase in proteinuria, podocyturia and width of foot process in NE group were ameliorated after treatment with 1,25(OH)2D3 for 8 weeks. The glomerulosclerotic index was significantly decreased in ND group when compared with NE group. The podocyte density in ND group (10.3±1.64 cells/glomerulus) was significantly higher than that in NE group (8.43±1.75 cells/glomerulus) (p=0.008). 1,25(OH)2D3 treatment could significantly up-regulate the mRNA and protein expressions of nephrin and podocin, and the protein expressions of α3β1 integrin and α/β-DG.
  
  
  CONCLUSIONS
  The expressions of nephrin, podocin, α3β1 integrin and α/β-DG were decreased in rats with nephropathy. However, 1,25(OH)2D3 treatment could significantly up-regulate the expressions of nephrin, podocin, α3β1 integrin and α/β-DG proteins which might suppress podocyte detachment and podocytopenia.
authors.affiliation: Department of Pediatrics, Wuhan General Hospital of Guangzhou Command, and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Min-shu
authors.initials: MS
authors.lastname: Zou
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Zhou
authors.forename: Guo-ming
authors.initials: GM
authors.lastname: Nie
authors.forename: Dong-sheng
authors.initials: DS
authors.lastname: Ding
authors.forename: Li-man
authors.initials: LM
authors.lastname: Luo
authors.forename: Hong-tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Wei-sun
authors.initials: WS
authors.lastname: He
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology / Q000627:therapeutic use*; D004317:Doxorubicin / Q000633:toxicity*; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D050199:Podocytes / Q000187:drug effects* / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004317:Doxorubicin; D002117:Calcitriol