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Am J Physiol Renal Physiol (November 30, 2004). doi:10.1152/ajprenal.00271.2004
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Submitted on July 23, 2004
Accepted on November 8, 2004

Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II

Denis Feliers1, Senthil Duraisamy1, Jeffrey L. Barnes1, Goutam Ghosh-Choudhury1, and Balakuntalam S. Kasinath1*

1 Department of Medicine/Nephrology, University of Texas Health Science Center, San Antonio, TX, USA; Department of Medicine, South Texas Veterans Health Care System, San Antonio, TX, USA

* To whom correspondence should be addressed. E-mail: kasinath{at}uthscsa.edu.

Angiotensin II regulates growth factor expression in the kidney. We investigated whether angiotensin II regulated VEGF synthesis in proximal tubular epithelial (MCT) cells. Angiotensin II (1 nM) increased VEGF protein expression within 5 min, the effect lasting for 30 min. There was no change in VEGF mRNA levels or mRNA stability, and transcription inhibitors did not affect angiotensin II induced VEGF expression. Regulation of VEGF translation was investigated. Polyribosomal analysis revealed selective enrichment of heavy ribosomes (polysomes) with VEGF mRNA transcripts compared to light ribosomes in angiotensin IItreated cells although distribution of GAPDH was unaltered. In vitro translation of total RNA from polysomal fractions showed selective increase in VEGF protein synthesis in angiotensin IItreated cells. Pre-incubation with LY294002, a PI 3-kinase inhibitor, or expression of dominant negative Akt prevented angiotensin II-stimulated increase in VEGF translation. Angiotensin II increased phosphorylation of eukaryotic initiation factor 4E (eIF4E) and its binding protein, 4EBP1, critical events that regulate the initiation phase of protein translation. Angiotensin II failed to increase VEGF mRNA translation in cells stably expressing phosphorylation mutant of 4EBP1. Our data illustrate that rapid increase in VEGF protein expression by angiotensin II is regulated at the initiation phase of translation of VEGF mRNA in renal epithelial cells. Regulation of VEGF translation by angiotensin II represents a novel pathway of renal response to injury.




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