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: 296/2/F427    most recent 90536.2008v1 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 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 (2) Citing Articles via Google Scholar Google Scholar Articles by Wei, X. F. Articles by Liang, M. Search for Related Content PubMed PubMed Citation Articles by Wei, X. F. Articles by Liang, M.

Advanced oxidation protein products induce mesangial cell perturbation through PKC-dependent activation of NADPH oxidase

¹Division of Nephrology, Nanfang Hospital, and ²Institute of Immunology, Southern Medical University, Guangzhou, China

Submitted 9 September 2008 ; accepted in final form 15 November 2008

Mesangial deposition of extracellular matrix (ECM) is a hallmark of several glomerular diseases including diabetic nephropathy. Accumulation of advanced oxidation protein products (AOPPs) has been found in diabetes and chronic kidney disease and linked to mesangial ECM deposition and progressive glomerulosclerosis in these disorders. Although emerging evidence implicates AOPPs as the renal pathogenic factors, the underlying mechanisms have not been investigated. Here, using cultured rat mesangial cells (MCs) as a model, we identify AOPPs as the important mediators for activation of MC NADPH oxidase. Exposure of MCs to AOPPs, through membrane-associated phosphorylation of PKC, induced rapid phosphorylation of cytosolic p47^phox and its membrane translocation, enhanced interaction of p47^phox with the membrane components p22^phox and Nox4, and increased expression of these key regulatory subunits of NADPH oxidase. Challenge with AOPPs triggered cytosolic superoxide generation, resulting in upregulation of fibronectin and collagen IV genes and proteins and overexpression of TGF-β1 via a PKC-NADPH oxidase-dependent pathway, as these downstream events were blocked by the inhibitors of PKC, inhibitors of NADPH oxidase, or the cytosolic superoxide scavenger. These data provide new information for understanding the molecular basis underlying AOPP-induced MC perturbation and might be a central step toward development of new interventions.

extracellular matrix

This article has been cited by other articles:

				N. M. Goldenberg and M. Silverman Rab34 and its effector munc13-2 constitute a new pathway modulating protein secretion in the cellular response to hyperglycemia Am J Physiol Cell Physiol, October 1, 2009; 297(4): C1053 - C1058. [Abstract] [Full Text] [PDF]