Effects of Endothelin-1 and Angiotensin-II on Extracellular Matrix Metabolism in a Rat Mesangial Cell Line, CRL-2573

The profibrogenic role of endothelin-1 (ET-1) and angiotensin-II (AT-II) in renal fibrosis remains disputed. We therefore studied the effect of ET-1 and AT-II on rat mesangial cells (CRL-2573), the major source of extracellular matrix proteins in the kidney. ET-1 stimulated DNA synthesis assessed by BrdU uptake in microtiter tetrazolium assay in a dose dependent manner, but AT-II did not. Proliferation of the mesangial cells by ET-1 was suppressed by 15% with BQ123, an endothelin receptor A antagonist, which suggested a significant role of the endothelin receptor A on growth stimulation. In the mesangial cells, ET-1 increased the mRNA expressions of procollagen α1 (I), transforming growth factor-β1, connective tissue growth factor, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-13 in dose dependent manners, whereas AT-II had exerted no effect on the expression of these mRNAs. These data suggested that ET-1 might be involved in renal fibrosis through the mesangial cell proliferation and/or the increase in fibrogenic cytokines.