title: Tacrolimus restores podocyte injury and stabilizes the expression of Cabin1 in 5/6 nephrectomized rats.
abstract: Podocyte injury is a vital factor, which induces massive proteinuria. Studies have shown that tacrolimus (TAC) protected podocyte via stabilizing cytoskeleton. Our latest study indicates that calcineurin binding protein 1 (Cabin1) undergoes nuclear translocation during podocytes injury. Whether TAC targets on Cabin1 during podocyte injury is still not clear. This study establishes non-immunological proteinuric model. To observe the effect of the treatment of TAC on Cabin1 expression in 5/6 nephrectomized rats. Sprague-Dawley rats were injected with TAC (0.2 mg/kg/day) for 4-8 weeks after 5/6 nephrectomy. Then, rats were sacrificed in the eighth week after operation, renal tissues were processed for morphological studies under light and electrical microscope. Cabin1 expression and distribution were detected by western blot and indirect immunofluorescence staining. In 5/6 nephrectomized rats, urinary protein excretion reached 90.2 ± 30.1 mg/24 h, glomerular sclerosis index and tubulointerstitial fibrosis score were significantly increased, and widespread of podocyte foot processes fusion was found. Moreover, Cabin1 protein expression was markedly increased, and its distribution became much more obviously in podocytes nuclei. In TAC treated rats, urinary protein excretion significantly decreased (44.9 ± 22.5 mg/24 h), glomerular sclerosis and tubulointerstitial fibrosis were alleviated, and podocyte foot processes fusion was inhibited. Furthermore, TAC alleviated the increased protein expression and abnormal distribution of Cabin1. In conclusion, TAC restores podocyte injury and stabilizes the expression of Cabin1. Cabin1 may become a new target to demonstrate the mechanism of TAC in podocyte injury.
authors.affiliation: a Department of Nephrology , The 2nd Affiliated Hospital of Guangzhou Medical University , Guangzhou , P.R. China ;
authors.forename: Yueqiang
authors.initials: Y
authors.lastname: Wen
authors.affiliation: b Department of General Medicine , The 3rd Affiliated Hospital of Sun Yat-Sen University , Guangzhou , P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Liu
authors.affiliation: a Department of Nephrology , The 2nd Affiliated Hospital of Guangzhou Medical University , Guangzhou , P.R. China ;
authors.forename: Peilan
authors.initials: P
authors.lastname: Zhou
authors.affiliation: a Department of Nephrology , The 2nd Affiliated Hospital of Guangzhou Medical University , Guangzhou , P.R. China ;
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Li
authors.affiliation: a Department of Nephrology , The 2nd Affiliated Hospital of Guangzhou Medical University , Guangzhou , P.R. China ;
authors.forename: Zebin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Department of Nephrology , The 2nd Affiliated Hospital of Guangzhou Medical University , Guangzhou , P.R. China ;
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Department of Nephrology , The 2nd Affiliated Hospital of Guangzhou Medical University , Guangzhou , P.R. China ;
authors.forename: Jianbo
authors.initials: J
authors.lastname: Liang
mesh_terms: D000818:Animals; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009842:Oligopeptides / Q000096:biosynthesis* / Q000187:drug effects*; D050199:Podocytes / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; C468309:cabin-1; D016559:Tacrolimus
keywords: Cabin1; Podocyte; Proteinuria; p53; tacrolimus