High glucose induced VEGF expression via PKC and ERK in glomerular podocytes.

Abstract:

:Podocytes are the major site of vascular endothelial growth factor (VEGF) production in the kidney, and up-regulation of VEGF plays a critical role in the progression of diabetic nephropathy. Using a differentiated mouse podocyte cell line, we investigated the roles of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) on the expression of VEGF under high glucose conditions. High glucose induced up-regulation of VEGF mRNA and protein expression in podocytes via activation of PKC (PKC-alpha and -betaII isoforms) and ERK. High glucose stimulated [(3)H]leucine incorporation in the podocytes. High glucose and the PKC stimulator, phorbol 12-myristate 13-acetate (PMA) induced activator protein-1 (AP-1)-dependent transcriptional activity and expression of VEGF. In addition, these phenomena were blocked by specific inhibitors of PKC (GF10902X) and ERK kinase (PD98059). These observations suggested that high glucose-induced VEGF expression in podocytes was largely mediated through PKC and ERK pathways that may be involved in diabetic nephropathy.

authors

Hoshi S,Nomoto K,Kuromitsu J,Tomari S,Nagata M

doi

10.1006/bbrc.2001.6138

subject

Has Abstract

pub_date

2002-01-11 00:00:00

pages

177-84

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X01961388

journal_volume

290

pub_type

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