HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/2/F255    most recent 00259.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Bijian, K. Articles by Cybulsky, A. V. Search for Related Content PubMed PubMed Citation Articles by Bijian, K. Articles by Cybulsky, A. V.

Extracellular matrix regulates glomerular epithelial cell survival and proliferation

Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada H3A 1A1

Submitted 22 July 2003 ; accepted in final form 6 October 2003

Glomerular epithelial cell (GEC) injury and apoptosis may contribute to sclerosis in glomerulonephritis. The present study addresses signals that regulate survival of GEC in culture and in the acute puromycin aminonucleoside nephrosis (PAN) model of GEC injury in vivo. Compared with GEC on plastic substratum, adhesion to collagen increased activation of focal adhesion kinase (FAK), c-Src, and ERK and facilitated survival (prevented apoptosis). GEC on plastic exhibited increased caspase-8 and -9 activities, increased expression of the proapoptotic protein, Bax, and decreased the antiapoptotic protein, Bcl-X_L, compared with collagen. Stable expression of constitutively active mutants of FAK (CD2-FAK) or MEK (R4F-MEK) activated the ERK pathway and supplanted the requirement of collagen for survival. In contrast, expression of a Ras mutant that activates phosphatidylinositol 3-kinase but blocks ERK activation or pharmacological inhibition of the ERK pathway decreased survival on collagen. Glomeruli isolated from rats with PAN revealed increased ₁-integrin expression, along with increased activation of FAK, c-Src, and ERK, compared with controls. EGF receptor activation was undetectable in PAN. Therefore, adhesion to collagen, resulting in activation of FAK and the Ras-ERK pathway, supports GEC survival. Analogous signals for GEC survival are activated in PAN.

apoptosis; glomerulonephritis; protein kinases; signal transduction

This article has been cited by other articles:

				A. V. Cybulsky, T. Takano, J. Papillon, K. Bijian, J. Guillemette, and C. R. J. Kennedy Glomerular epithelial cell injury associated with mutant {alpha}-actinin-4 Am J Physiol Renal Physiol, October 1, 2009; 297(4): F987 - F995. [Abstract] [Full Text] [PDF]

				N. Engineer, S. R. Sooranna, Z. Liang, P. R. Bennett, and M. R. Johnson Influence of Extracellular Matrix on Cytokine Stimulated Pro-labour Gene Expression in Human Uterine Myocytes Reproductive Sciences, November 1, 2008; 15(9): 950 - 960. [Abstract] [PDF]

				H. J. Han, M. J. Lim, Y. J. Lee, J. H. Lee, I. S. Yang, and M. Taub Uric acid inhibits renal proximal tubule cell proliferation via at least two signaling pathways involving PKC, MAPK, cPLA2, and NF-{kappa}B Am J Physiol Renal Physiol, January 1, 2007; 292(1): F373 - F381. [Abstract] [Full Text] [PDF]

				L. Aoudjit, A. Potapov, and T. Takano Prostaglandin E2 promotes cell survival of glomerular epithelial cells via the EP4 receptor Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1534 - F1542. [Abstract] [Full Text] [PDF]

				W. Hao, T. Takano, J. Guillemette, J. Papillon, G. Ren, and A. V. Cybulsky Induction of Apoptosis by the Ste20-like Kinase SLK, a Germinal Center Kinase That Activates Apoptosis Signal-regulating Kinase and p38 J. Biol. Chem., February 10, 2006; 281(6): 3075 - 3084. [Abstract] [Full Text] [PDF]

				K. Bijian, T. Takano, J. Papillon, L. Le Berre, J.-L. Michaud, C. R. J. Kennedy, and A. V. Cybulsky Actin cytoskeleton regulates extracellular matrix-dependent survival signals in glomerular epithelial cells Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1313 - F1323. [Abstract] [Full Text] [PDF]

				A. V. Cybulsky, T. Takano, J. Papillon, K. Bijian, and J. Guillemette Activation of the extracellular signal-regulated kinase by complement C5b-9 Am J Physiol Renal Physiol, September 1, 2005; 289(3): F593 - F603. [Abstract] [Full Text] [PDF]