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Reduction of Slit Diaphragm-associated Molecules by Sirolimus: Is it Enough to Induce Proteinuria?

Authors
 B.S. Kim  ;  J.G. Lee  ;  Y. Cho  ;  S.H. Song  ;  K.H. Huh  ;  M.S. Kim  ;  Y.S. Kim 
Citation
 TRANSPLANTATION PROCEEDINGS, Vol.5(49) : 1165-1169, 2017 
Journal Title
TRANSPLANTATION PROCEEDINGS
ISSN
 0041-1345 
Issue Date
2017
MeSH
Animals ; Immunosuppressive Agents/toxicity* ; Kidney/drug effects* ; Male ; Mice, Inbred C57BL ; Proteinuria/chemically induced* ; Sirolimus/toxicity*
Abstract
Sirolimus (SRL), a mammalian target of rapamycin inhibitor, is widely used in transplantation, but the mechanisms whereby it induces adverse effects, such as proteinuria and edema, remain unclear. To determine whether isolated SRL induces proteinuria or not, the authors intraperitoneally injected C57BL/6 mice with different doses of SRL (0 mg/[kg·d], 3 mg/[kg·d], 10 mg/[kg·d], or 30 mg/[kg·d]) for 24 days. Urinary albumin excretion was then quantified using a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured using a single dry-film chemistry auto-analyzer. The mRNA expression levels of various genes were also measured by polymerase chain reaction. Urinary albumin was not detected in the SRL-treated mice, but serum creatinine levels were found to increase dose-dependently and were significantly higher in the animals treated with 30 mg/kg of SRL than in untreated controls. Glomerular mRNA expression profiling showed down-regulations of podocyte-related genes (Wilms tumor 1, synaptopodin, nephrin, CD2-associated protein, and podocin) and of transforming growth factor-beta (a marker of fibrosis) in sirolimus-treated mice. In addition, expressions of the antiapoptotic genes Bcl-2 and Bcl-xL were also down-regulated. Furthermore, the protein levels of these genes in mice kidney were also decreased by sirolimus. Although sirolimus treatment reduced the expressions of slit diaphragm-associated molecules and increased serum creatinine levels, it failed to induce proteinuria. Our findings indicate that proteinuria is not induced by isolated SRL treatment. Further studies are required to identify conditions in which sirolimus induces proteinuria.
Full Text
https://www.sciencedirect.com/science/article/pii/S0041134517302361
DOI
10.1016/j.transproceed.2017.03.021
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Lee, Jae Geun(이재근) ORCID logo https://orcid.org/0000-0002-6722-0257
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160340
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