Abstract | BACKGROUND/AIMS: METHODS: Rats were intravenously injected once on day 0 with 100 mg/kg of PAN and received daily subcutaneous injections of MZR at a dose of 10 mg/kg from days 0 to 14. Cultured podocytes were pretreated with 50 microg/ml of MZR and then treated with 30 microg/ml of PAN. RESULTS: In rat PAN nephrosis, treatment with MZR from days 0 to 14 almost completely inhibited proteinuria. Immunofluorescence staining of nephrin was diminished, showing a discontinuous pattern in saline-treated PAN rats. In contrast, MZR treatment resulted in maintenance of a normal linear pattern. In cultured podocytes exposed to PAN, the percentages of viable cells were significantly increased with MZR treatment. The protective effect of MZR on PAN-induced podocyte injury was independent of inosine 5'-monophosphate dehydrogenase that is a known target enzyme of MZR as an immunosuppressant. MZR reduced PAN-induced integrin-linked kinase activation (ILK) and phosphorylation of glycogen synthase kinase-3beta ( GSK3beta) in vivo and in vitro. CONCLUSION: MZR directly prevents PAN-induced podocyte injury, possibly by affecting signaling cascades involving ILK and GSK3beta.
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Authors | Shigeru Takeuchi, Keiju Hiromura, Mai Tomioka, Satoshi Takahashi, Toru Sakairi, Akito Maeshima, Yoriaki Kaneko, Takashi Kuroiwa, Yoshihisa Nojima |
Journal | Nephron. Experimental nephrology
(Nephron Exp Nephrol)
Vol. 116
Issue 1
Pg. e3-10
( 2010)
ISSN: 1660-2129 [Electronic] Switzerland |
PMID | 20502051
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2010 S. Karger AG, Basel. |
Chemical References |
- Immunosuppressive Agents
- Membrane Proteins
- Ribonucleosides
- nephrin
- mizoribine
- Puromycin Aminonucleoside
- IMP Dehydrogenase
- integrin-linked kinase
- Protein Serine-Threonine Kinases
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Topics |
- Animals
- IMP Dehydrogenase
(antagonists & inhibitors, metabolism)
- Immunosuppressive Agents
(therapeutic use)
- Male
- Membrane Proteins
(biosynthesis)
- Nephrosis
(chemically induced, drug therapy)
- Podocytes
(drug effects)
- Protein Serine-Threonine Kinases
(metabolism)
- Puromycin Aminonucleoside
(antagonists & inhibitors)
- Rats
- Rats, Wistar
- Ribonucleosides
(therapeutic use)
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