Yonago Acta medica 2006;49:29-37
Effects of Endothelin-1 and Angiotensin-II on Extracellular Matrix Metabolism in a Rat Mesangial Cell Line, CRL-2573
Satoru Yamamoto, Masahiko Koda, Masaru Ueki, Chishio Munemura, Satoko Maeta and Yoshikazu Murawaki
Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504 Japan
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.
Key words: angiotensin-II; endothelin-1; extracellular matrix metabolism; mesangial cell