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

 B.S. Kim  ;  J.G. Lee  ;  Y. Cho  ;  S.H. Song  ;  K.H. Huh  ;  M.S. Kim  ;  Y.S. Kim 
 Transplantation Proceedings, Vol.5(49) : 1165-1169, 2017 
Journal Title
 Transplantation Proceedings 
Issue Date
Animals ; Immunosuppressive Agents/toxicity* ; Kidney/drug effects* ; Male ; Mice, Inbred C57BL ; Proteinuria/chemically induced* ; Sirolimus/toxicity*
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.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김명수(Kim, Myoung Soo) ORCID logo https://orcid.org/0000-0002-8975-8381
김범석(Kim, Beom Seok) ORCID logo https://orcid.org/0000-0002-5732-2583
김유선(Kim, Yu Seun) ORCID logo https://orcid.org/0000-0002-5105-1567
이재근(Lee, Jae Geun) ORCID logo https://orcid.org/0000-0002-6722-0257
허규하(Huh, Kyu Ha) ORCID logo https://orcid.org/0000-0003-1364-6989
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