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Cell Mol Biol (Noisy-le-grand). 2019 Jan 31;65(1):84-88.

Upregulation of Tumor Susceptibility Gene 101 (TSG101) by mechanical stress in podocytes.

Author information

1
Dept. of Anatomy, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
2
Center for Biomedicine and Medical Technology (CBMT), Neuroanatomy, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
3
Medical Research Center (ZMF), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
4
Dept. of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI 48109-5676, USA.
5
Dept. of Anatomy and Cell Biology, University Medicine Greifswald, D-17487 Greifswald, Germany.

Abstract

Elevated mechanical stress in glomerular hypertension is thought to damage podocytes, the loss of which leads to development of glomerulosclerosis. Applying cDNA array analysis to mechanically stressed podocytes, we have recently identified TSG101 as a stretch-induced candidate gene among others. TSG101, which is part of the ESCRT-I complex, is involved in multivesicular body (MVB) formation. Here we demonstrate that TSG101 mRNA is strongly upregulated in conditionally immortalized mouse podocytes by cyclic mechanical stress. Differentiation of podocytes does not affect TSG101 mRNA levels. TSG101 immunofluorescence is distributed in a vesicular pattern in podocytes, the staining intensity being enhanced by mechanical stress. In DOCA/salt treated rats, a model of glomerular hypertension, glomerular TSG101 mRNA levels are elevated, and an increased number of MVBs is observed by electron microscopy in podocyte processes. Our data demonstrate that mechanical stress upregulates TSG101 in podocytes, suggesting that glomerular hypertension enhances sorting of cell surface proteins and their ligands into the degradative pathway in podocytes.

KEYWORDS:

DOCA/salt hypertension; Glomerular hypertension; Mechanical stress; Multivesicular bodies; Podocytes.; TSG101

PMID:
30782301

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