Angiotensin II activates plasminogen activator inhibitor-I promoter in renal tubular epithelial cells via the AT1 receptor

Fintha, A. and Sebe, A. and Masszi, A. and Terebessy, T. and Huszár, T. and Rosivall, L. and Mucsi, I. (2007) Angiotensin II activates plasminogen activator inhibitor-I promoter in renal tubular epithelial cells via the AT1 receptor. Acta Physiologica Hungarica, 94 (1-2). pp. 19-30. ISSN 0231-424X

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Abstract

Background: Plasminogen activator inhibitor-1 (PAI-1) regulates normal extracellular matrix (ECM) metabolism and it is a key regulator of the fibrotic process. Both angiotensin II (Ang II) and angiotensin IV (Ang IV) have been reported to stimulate PAI-1 expression. It is not known how PAI-1 expression is regulated by the renin-angiotensin system (RAS) in renal tubular cells. Methods: To dissect signaling mechanisms contributing to the up-regulation of the PAI-1 promoter, porcine proximal tubular cells stably expressing the rabbit AT 1 receptor (LLC-PK/AT 1 ) were transiently transfected with a luciferase reporter construct containing the PAI-1 promoter. Promoter activation was assessed by measuring luciferase activity from cell lysates. Results: Ang II dose-dependently stimulated the transcriptional activity of the PAI-1 promoter in renal proximal tubular cells whereas Ang IV had no consistent effect on the promoter activity. Neither inhibition of the Extracellular Signal Regulated Kinase (ERK) cascade nor inhibition of the c-Jun-N- terminal Kinase (JNK) pathway did reduce the stimulation of the PAI-1 promoter by Ang II. However, genistein, a tyrosine kinase inhibitor blocked the effect of Ang II. Conclusion: Ang II but not Ang IV activates the PAI-1 promoter in renal proximal tubular cells and this effect is mediated by tyrosine kinases.

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