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Sci Rep. 2018 Mar 22;8(1):5061. doi: 10.1038/s41598-018-23278-6.

Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis.

Author information

1
Medical Innovation Research, TMK Project, Kyoto University Graduate School of Medicine, Kyoto, Japan.
2
Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
3
Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
4
Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
5
Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Faculty of Medicine, Tokyo, Japan.
6
Medical Innovation Research, TMK Project, Kyoto University Graduate School of Medicine, Kyoto, Japan. kasanuma@chiba-u.jp.
7
Division of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan. kasanuma@chiba-u.jp.
8
Department of Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan. kasanuma@chiba-u.jp.

Abstract

Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman's capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.

PMID:
29567961
PMCID:
PMC5864960
DOI:
10.1038/s41598-018-23278-6
[Indexed for MEDLINE]
Free PMC Article

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