BRADYKININ STIMULATES C-FOS EXPRESSION, AP-1-DNA BINDING-ACTIVITY ANDPROLIFERATION OF RAT GLOMERULAR MESANGIAL CELLS

An important role for bradykinin (BK) in nephrogenesis has been sugges ted based on impairment of renal growth in developing rats treated wit h a kinin antagonist. However. direct effects of BK on renal cell mito genesis have not been reported. In the present study, we examined the mitogenic effects of BK on cultured rat mesangial cells Transcripts en coding BK-B-2 receptors were detected in quiescent and proliferating m esangial cells by reverse transcription-coupled polymerase chain react ion. 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 (H-3- thymidine incorporation into DNA) and cell number. BK-induced DNA synt hesis was preceded by activation of c-fos gene expression and both of these effects were inhibited by Hoe-140, a specific BK-B-2 antagonist. Electrophoretic gel mobility shift assays revealed enhanced binding o f AP-1 complexes to a consensus AP-1 DNA sequence in BK-stimulated cel ls. Gel supershift assays confirmed that the AP-1 complexes contained the fos protein. These data document a direct mitogenic effect of BK, acting on B-2 receptors, on mesangial cells.