title: Role of calcineurin (CN) in kidney glomerular podocyte: CN inhibitor ameliorated proteinuria by inhibiting the redistribution of CN at the slit diaphragm.
abstract: Although calcineurin (CN) is distributed in many cell types and functions in regulating cell functions, the precise roles ofCNremained in each type of the cells are not well understood yet. ACNinhibitor (CNI) has been used for steroid-resistant nephrotic syndrome. ACNIis assumed to ameliorate proteinuria by preventing the overproduction of T-cell cytokines. However, recent reports suggest thatCNIhas a direct effect on podocyte. It is accepted that a slit diaphragm (SD), a unique cell-cell junction of podocytes, is a critical barrier preventing a leak of plasma protein into urine. Therefore, we hypothesized thatCNIhas an effect on theSD In this study, we analyzed the expression ofCNin physiological and in the nephrotic model caused by the antibody against nephrin, a critical component of theSD We observed thatCNis expressed at theSDin normal rat and human kidney sections and has an interaction with nephrin. The staining ofCNat theSDwas reduced in the nephrotic model, whileCNactivity in glomeruli was increased. We also observed that the treatment with tacrolimus, aCNI, in this nephrotic model suppressed the redistribution ofCN, nephrin, and otherSDcomponents and ameliorated proteinuria. These observations suggested that the redistribution and the activation ofCNmay participate in the development of theSDinjury.
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Wakamatsu
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Fukusumi
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Department of Pediatrics, Niigata City General Hospital, Niigata, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.affiliation: Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan kawachi@med.niigata-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000151:congenital / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D050199:Podocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D021381:Protein Transport; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017208:Rats, Wistar; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D065095:Calcineurin Inhibitors; D008565:Membrane Proteins; C113267:nephrin; D019703:Calcineurin; C525673:PPP3CA protein, human; D016559:Tacrolimus
keywords: calcineurin; podocyte; proteinuria; slit diaphragm