Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2014 Apr 18;446(4):1190-6. doi: 10.1016/j.bbrc.2014.03.088. Epub 2014 Mar 26.

Transient increase in proteinuria, poly-ubiquitylated proteins and ER stress markers in podocyte-specific autophagy-deficient mice following unilateral nephrectomy.

Author information

1
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
2
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
3
Division of Genome Research, Research Institute for Diseases of Old Ages, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
4
Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
5
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: yasu@juntendo.ac.jp.

Abstract

Previous studies have revealed that podocytes normally can be associated with a very high degree of autophagic activity, and that a lack of autophagic activity in podocytes is associated with susceptibility to disease and to late-onset glomerulosclerosis. In the present study, we conducted unilateral nephrectomy as a surgical model for acute nephron reduction. First, using GFP-LC3 transgenic mice to monitor autophagy, we found that glomerular autophagy could be transiently suppressed by surgery, but that it was restored quickly. To further explore the significance of podocyte autophagy after unilateral nephrectomy, we investigated podocyte-specific Atg7-deficient mice. The knockout mice exhibited no pathological phenotype compared with wild-type mice before nephrectomy. However, 1 day after nephrectomy, significantly higher levels of proteinuria and ultrastructural changes that included foot process effacement and a significant reduction in podocyte number were detected in mice harboring Atg7-deficient podocytes. Moreover, biochemical and immunohistochemical analyses showed a robust increase in polyubiquitin levels and ER stress markers in the glomeruli of the mice with autophagy-deficient podocytes. These results show the importance of the autophagic process in podocytes for maintaining a normal degree of filtration function during the adaptation to compensatory kidney hypertrophy following unilateral nephrectomy.

KEYWORDS:

Atg7; Autophagy; ER stress; Nephrectomy; Podocyte; Ubiquitin

PMID:
24680677
DOI:
10.1016/j.bbrc.2014.03.088
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center