The β isoform of GSK3 mediates podocyte autonomous injury in proteinuric glomerulopathy

The Journal of Pathology
Changbin LiR Gong

Abstract

Converging evidence points to glycogen synthase kinase (GSK) 3 as a key player in the pathogenesis of podocytopathy and proteinuria. However, it remains unclear if GSK3 is involved in podocyte autonomous injury in glomerular disease. In normal kidneys, the β isoform of GSK3 was found to be the major GSK3 expressed in glomeruli and intensely stained in podocytes. GSK3β expression in podocytes was markedly elevated in experimental or human proteinuric glomerulopathy. Podocyte-specific somatic ablation of GSK3β in adult mice attenuated proteinuria and ameliorated podocyte injury and glomerular damage in experimental adriamycin (ADR) nephropathy. Mechanistically, actin cytoskeleton integrity in podocytes was largely preserved in GSK3β knockout mice following ADR insult, concomitant with a correction of podocyte hypermotility and lessened phosphorylation and activation of paxillin, a focal adhesion-associated adaptor protein. In addition, GSK3β knockout diminished ADR-induced NFκB RelA/p65 phosphorylation selectively at serine 467; suppressed de novo expression by podocytes of NFκB-dependent podocytopathic mediators, including B7-1, cathepsin L, and MCP-1; but barely affected the induction of NFκB target pro-survival factors, such a...Continue Reading

References

Feb 9, 1996·Cell·D A Lauffenburger, A F Horwitz
Mar 1, 1996·The Journal of Experimental Medicine·J ZhaoL H Glimcher
Jan 1, 1997·Kidney & Blood Pressure Research·W Kriz
Dec 26, 2001·Chemical Reviews·A AliJ R Woodgett
Jun 18, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Robert F Schwabe, David A Brenner
Sep 6, 2002·The American Journal of Pathology·Minoru TakemotoChrister Betsholtz
Jan 1, 2004·Drug News & Perspectives·Jean Van Wauwe, Burkhard Haefner
Jan 27, 2004·Nature Cell Biology·Donna J WebbAlan F Horwitz
Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
Jun 3, 2004·Nature Reviews. Drug Discovery·Philip Cohen, Michel Goedert
Sep 14, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carla IacobiniGiuseppe Pugliese
Sep 1, 2006·Journal of the American Society of Nephrology : JASN·Chun-Liang LinFeng-Sheng Wang
Nov 24, 2006·Cell Communication and Signaling : CCS·Nancy Abou ZeidBrigitte Boyer
Apr 9, 2008·Physiological Reviews·Börje HaraldssonWilliam M Deen
Aug 13, 2008·Molecular and Cellular Biology·Satish PatelJames R Woodgett
Aug 30, 2008·Journal of the American Society of Nephrology : JASN·Rachel LennonMoin A Saleem
Sep 13, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R GongL D Dworkin
Apr 16, 2009·British Journal of Pharmacology·Geetha Vani RayasamAbhijit Ray
Jul 8, 2009·Nature Reviews. Nephrology·Jaakko Patrakka, Karl Tryggvason
Jul 25, 2009·Journal of the American Society of Nephrology : JASN·Chunsun DaiYouhua Liu
Aug 20, 2009·Mini Reviews in Medicinal Chemistry·Félix HernándezNieves Villanueva
Aug 29, 2009·Journal of the American Society of Nephrology : JASN·Aoife Waters, Ania Koziell
Oct 20, 2009·Trends in Immunology·Eléonore BeurelRichard S Jope
Nov 20, 2009·Kidney International·Peter Mundel, Jochen Reiser
Feb 2, 2010·Free Radical Biology & Medicine·Chun ZhangPin-Lan Li
Jun 26, 2010·Journal of the American Society of Nephrology : JASN·János Peti-Peterdi, Arnold Sipos
Aug 4, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yan GeRujun Gong
Dec 24, 2010·Nephrology·Vincent W S Lee, David C H Harris
Aug 2, 2011·Nature Medicine·Changli WeiJochen Reiser
Sep 7, 2011·The American Journal of Pathology·Krishna M BoiniPin-Lan Li
Nov 24, 2011·Frontiers in Molecular Neuroscience·Oksana Kaidanovich-Beilin, James Robert Woodgett
Nov 12, 2013·The New England Journal of Medicine·Chih-Chuan YuPeter Mundel

❮ Previous
Next ❯

Citations

Oct 14, 2016·Journal of Translational Medicine·H TrimarchiA Ortiz
Sep 25, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Li-Qin PengLi-Jun Yao
Apr 2, 2020·Cells·Leonie HoffmeisterRené Huber
Sep 6, 2020·Molecular Neurobiology·Md Tanvir KabirMohamed M Abdel-Daim
Oct 20, 2020·American Journal of Physiology. Renal Physiology·Nehaben A GujaratiSandeep K Mallipattu
Dec 22, 2020·The Journal of Experimental Medicine·Shuai HuZhihong Liu
Dec 1, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Firdos Ahmad, James R Woodgett
Jul 22, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Wei-Lun LiuHeng-Liang Lin

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.