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Vol. 65 No. 1: Issue 1

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

https://doi.org/10.14715/cmb/2019.65.1.15
Masataka Sunohara
Dept. of Anatomy, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
Wilhelm Kriz
Center for Biomedicine and Medical Technology (CBMT), Neuroanatomy, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
Bettina Kränzlin
Medical Research Center (ZMF), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
Matthias Kretzler
Dept. of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI 48109-5676, USA
Norbert Gretz
Medical Research Center (ZMF), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
Karlhans Endlich
Dept. of Anatomy and Cell Biology, University Medicine Greifswald, D-17487 Greifswald, Germany
Nicole Endlich
Dept. of Anatomy and Cell Biology, University Medicine Greifswald, D-17487 Greifswald, Germany

Corresponding Author(s) : Masataka Sunohara

ma-suno@tky.ndu.ac.jp

Cellular and Molecular Biology, Vol. 65 No. 1: Issue 1

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

TSG101 Mechanical stress Glomerular hypertension DOCA/salt hypertension Multivesicular bodies Podocytes.
Sunohara, M., Kriz, W., Kränzlin, B., Kretzler, M., Gretz, N., Endlich, K., & Endlich, N. (2019). Upregulation of Tumor Susceptibility Gene 101 (TSG101) by mechanical stress in podocytes. Cellular and Molecular Biology, 65(1), 84–88. https://doi.org/10.14715/cmb/2019.65.1.15
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Author Biography

Masataka Sunohara, Dept. of Anatomy, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
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