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: Ayako Wakamatsu, Yoshiyasu Fukusumi, Eriko Hasegawa, Masayuki Tomita, Toru Watanabe, Ichiei Narita, Hiroshi Kawachi
• Journal: Physiological reports (Physiol Rep) Vol. 4 Issue 6 (Mar 2016) ISSN: 2051-817X [Print] United States
• PMID: 27009276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Chemical References

• Antibodies, Monoclonal
• Calcineurin Inhibitors
• Membrane Proteins
• nephrin
• Calcineurin
• PPP3CA protein, human
• Tacrolimus

Topics

• Animals
• Antibodies, Monoclonal
• Calcineurin (metabolism)
• Calcineurin Inhibitors (pharmacology)
• Cell Line
• Child
• Disease Models, Animal
• Female
• Humans
• Intercellular Junctions (drug effects, enzymology, pathology)
• Male
• Membrane Proteins (immunology, metabolism)
• Mice
• Nephrotic Syndrome (chemically induced, congenital, drug therapy, enzymology, pathology)
• Podocytes (drug effects, enzymology, pathology)
• Protein Transport
• Proteinuria (chemically induced, drug therapy, enzymology, pathology)
• Rats, Wistar
• Tacrolimus (pharmacology)
• Time Factors