Bradykinin stimulates c-fos expression, AP-1-DNA binding activity and proliferation of rat glomerular mesangial cells

Kidney International
S S el-DahrW H Baricos

Abstract

An important role for bradykinin (BK) in nephrogenesis has been suggested based on impairment of renal growth in developing rats treated with a kinin antagonist. However, direct effects of BK on renal cell mitogenesis have not been reported. In the present study, we examined the mitogenic effects of BK on cultured rat mesangial cells. Transcripts encoding BK-B2 receptors were detected in quiescent and proliferating mesangial cells by reverse transcription-coupled polymerase chain reaction. In quiescent mesangial cell cultures (0.5% FCS for 48 hr), BK (10(-9) to 10 (-7)M) caused a significant increase in DNA synthesis (3H-thymidine incorporation into DNA) and cell number. BK-induced DNA synthesis was preceded by activation of c-fos gene expression and both of these effects were inhibited by Hoe-140, a specific BK-B2 antagonist. Electrophoretic gel mobility shift assays revealed enhanced binding of AP-1 complexes to a consensus AP-1 DNA sequence in BK-stimulated cells. Gel supershift assays confirmed that the AP-1 complexes contained the fos protein. These data document a direct mitogenic effect of BK, acting on B2 receptors, on mesangial cells.

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Citations

Jan 24, 1998·European Journal of Pharmacology·J A Ruiz-GinésD Rodríguez-Puyol
Jul 12, 2002·Kidney International·Celine AlricJean-Pierre Girolami
Sep 12, 1998·Kidney International·S C DivenR M Goldblum
Nov 19, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Ilyas TuncerIrfan Bayram
Jan 20, 2010·Journal of Receptor and Signal Transduction Research·Jerry G WebbAyad A Jaffa
Dec 31, 1997·Microscopy Research and Technique·S S el-Dahr
Mar 9, 2007·Journal of the American Society of Nephrology : JASN·Bing ShenSamir S El-Dahr
Nov 9, 2006·American Journal of Physiology. Renal Physiology·Wanke ZhangBin-Xian Zhang
Aug 30, 2008·American Journal of Physiology. Renal Physiology·Samir S El-DahrSusana Dipp
Jan 22, 1998·The American Journal of Physiology·A A JaffaR K Mayfield
Sep 8, 1998·The American Journal of Physiology·S S El-DahrW H Baricos
Sep 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·L YauP Zahradka
Jul 16, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Izumi HayashiMasataka Majima

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