title: Effects of 22-oxa-calcitriol on podocyte injury in adriamycin-induced nephrosis.
abstract: BACKGROUND
  In various animal studies, vitamin D has been shown to have a significant effect on reduction of proteinuria and the progression of kidney disease. However, little is known on its renoprotective effect in adriamycin (ADR)-induced nephrosis mice. The present study was intended to determine the therapeutic benefit of 22-oxa-calcitriol (OCT), a vitamin D analog, in reducing proteinuria and its renoprotective effect, i.e. preventing podocyte injury on ADR-induced nephrosis mice.
  
  
  METHODS
  Three experimental groups were used as follows: (1) nephrosis mice, established by a single intravenous injection of ADR; (2) ADR+OCT mice, nephrosis mice treated with OCT, and (3) mice treated only with OCT as the control group. Podocyte injury was assessed by podocyte apoptosis using the TUNEL assay, podocyte counting, podocyte-specific expressed protein by immunofluorescence and Western blot analysis, and foot process effacement using electron microscopy.
  
  
  RESULTS
  Lower proteinuria was observed in ADR+OCT mice. Improvement in glomerulosclerosis and interstitial fibrosis, and prevention of glomerular hyperfiltration were observed in ADR+OCT mice. Immunofluorescence and Western blot analyses showed restoration of downregulated expression of nephrin, CD2AP and podocin. Nevertheless, dendrin expression was not restored. An insignificant reduction in podocyte numbers was found in ADR+OCT mice. Complete foot process effacement was partially prevented in ADR+OCT mice.
  
  
  CONCLUSIONS
  The results indicate that OCT reduces podocyte injury and has renoprotective effects in ADR nephrosis mice.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Aida
authors.initials: A
authors.lastname: Lydia
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Kanae
authors.initials: K
authors.lastname: Nonaka
authors.forename: Miyuki
authors.initials: M
authors.lastname: Takagi
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jeong
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kodama
authors.forename: Rin
authors.initials: R
authors.lastname: Asao
authors.forename: Etsuko
authors.initials: E
authors.lastname: Asanuma
authors.forename: Wiguno
authors.initials: W
authors.lastname: Prodjosudjadi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology*; D005260:Female; D005355:Fibrosis / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007674:Kidney Diseases / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D009401:Nephrosis / Q000188:drug therapy*; D050199:Podocytes / Q000187:drug effects / Q000473:pathology*; D011507:Proteinuria / Q000097:blood; D012598:Sclerosis / Q000097:blood; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives
chemical_list: D000903:Antibiotics, Antineoplastic; D014807:Vitamin D; D004317:Doxorubicin; D002117:Calcitriol; C051883:maxacalcitol