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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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References
  1. Endlich N, Endlich K (2012) The challenge and response of podocytes to glomerular hypertension. Semin Nephrol 32: 327-341.
  2. Kriz W, Lemley KV (2015) A Potential Role for Mechanical Forces in the Detachment of Podocytes and the Progression of CKD. J Am Soc Nephrol 26: 258-269.
  3. Kriz W, Endlich K (2005) Hypertrophy of podocytes: a mechanism to cope with increased glomerular capillary pressures? Kidney Int 67: 373-374.
  4. Endlich N, Kress KR, Reiser J, Uttenweiler D, Kriz W, et al. (2001) Podocytes respond to mechanical stress in vitro. Journal of the American Society of Nephrology : JASN 12: 413-422.
  5. Endlich N, Sunohara M, Nietfeld W, Wolski EW, Schiwek D, et al. (2002) Analysis of differential gene expression in stretched podocytes: osteopontin enhances adaptation of podocytes to mechanical stress. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16: 1850-1852.
  6. Petermann AT, Hiromura K, Blonski M, Pippin J, Monkawa T, et al. (2002) Mechanical stress reduces podocyte proliferation in vitro. Kidney international 61: 40-50.
  7. Petermann AT, Pippin J, Durvasula R, Pichler R, Hiromura K, et al. (2005) Mechanical stretch induces podocyte hypertrophy in vitro. Kidney international 67: 157-166.
  8. Martineau LC, McVeigh LI, Jasmin BJ, Kennedy CR (2004) p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton. American journal of physiology Renal physiology 286: F693-701.
  9. Friedrich C, Endlich N, Kriz W, Endlich K (2006) Podocytes are sensitive to fluid shear stress in vitro. American journal of physiology Renal physiology 291: F856-865.
  10. Durvasula RV, Petermann AT, Hiromura K, Blonski M, Pippin J, et al. (2004) Activation of a local tissue angiotensin system in podocytes by mechanical strain. Kidney international 65: 30-39.
  11. Durvasula RV, Shankland SJ (2005) Mechanical strain increases SPARC levels in podocytes: implications for glomerulosclerosis. American journal of physiology Renal physiology 289: F577-584.
  12. Faour WH, Thibodeau JF, Kennedy CR (2010) Mechanical stretch and prostaglandin E2 modulate critical signaling pathways in mouse podocytes. Cellular signalling 22: 1222-1230.
  13. Lewko B, Endlich N, Kriz W, Stepinski J, Endlich K (2004) C-type natriuretic peptide as a podocyte hormone and modulation of its cGMP production by glucose and mechanical stress. Kidney international 66: 1001-1008.
  14. Li L, Cohen SN (1996) Tsg101: a novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells. Cell 85: 319-329.
  15. Babst M, Odorizzi G, Estepa EJ, Emr SD (2000) Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. Traffic 1: 248-258.
  16. Raiborg C, Rusten TE, Stenmark H (2003) Protein sorting into multivesicular endosomes. Curr Opin Cell Biol 15: 446-455.
  17. Slagsvold T, Pattni K, Malerod L, Stenmark H (2006) Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol 16: 317-326.
  18. Bishop N, Horman A, Woodman P (2002) Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol 157: 91-101.
  19. Welsch T, Endlich N, Kriz W, Endlich K (2001) CD2AP and p130Cas localize to different F-actin structures in podocytes. American journal of physiology Renal physiology 281: F769-777.
  20. Kretzler M, Koeppen-Hagemann I, Kriz W (1994) Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat. Virchows Archiv : an international journal of pathology 425: 181-193.
  21. Dworkin LD, Hostetter TH, Rennke HG, Brenner BM (1984) Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. The Journal of clinical investigation 73: 1448-1461.
  22. Futter CE, Pearse A, Hewlett LJ, Hopkins CR (1996) Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes. J Cell Biol 132: 1011-1023.
  23. Piper RC, Katzmann DJ (2007) Biogenesis and function of multivesicular bodies. Annu Rev Cell Dev Biol 23: 519-547.
  24. Kriz W, Shirato I, Nagata M, LeHir M, Lemley KV (2013) The podocyte's response to stress: the enigma of foot process effacement. Am J Physiol Renal Physiol 304: F333-347.
  25. Huber TB, Edelstein CL, Hartleben B, Inoki K, Jiang M, et al. (2012) Emerging role of autophagy in kidney function, diseases and aging. Autophagy 8: 1009-1031.
  26. Riediger F, Quack I, Qadri F, Hartleben B, Park JK, et al. (2011) Prorenin receptor is essential for podocyte autophagy and survival. J Am Soc Nephrol 22: 2193-2202.
  27. Kerjaschki D, Exner M, Ullrich R, Susani M, Curtiss LK, et al. (1997) Pathogenic antibodies inhibit the binding of apolipoproteins to megalin/gp330 in passive Heymann nephritis. J Clin Invest 100: 2303-2309.
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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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