
Effects of Specific Endothelin‐1 Receptor Antagonists on Proliferation and Fibronectin Production of Glomerular Mesangial Cells Stimulated with Angiotensin II
Author(s) -
Kuo HungTien,
Kuo MeiChuan,
Chen HungChun,
Shin ShyiJang
Publication year - 2006
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/s1607-551x(09)70325-0
Subject(s) - angiotensin ii , fibronectin , medicine , endocrinology , endothelin 1 , receptor , receptor antagonist , mesangial cell , cytokine , endothelin receptor , kidney , antagonist , biology , microbiology and biotechnology , extracellular matrix
Angiotensin II (Ang‐II) is a potent vasoactive hormone, which plays an important role in the pathogenesis of glomerulosclerosis. Ang‐II activates many cytokine systems in the kidney. Recent studies indicate that Ang‐II is closely related to the activation of the endothelin‐1 (ET‐1) system. The present study was designed to measure the [H 3 ]‐thymidine uptake and fibronectin production of cultured rat mesangial cells stimulated with Ang‐II, and to evaluate the effects of specific ET‐1 receptor antagonists, BQ123 (type A receptor antagonist) and IRL1038 (type B receptor antagonist) on the cells. ET‐1 was measured by radioimmunoassay and fibronectin by Western blot analysis. The results were as follows: (1) Ang‐II enhanced ET‐1 production, [H 3 ]‐thymidine uptake, number of cells, and fibronectin production of mesangial cells; (2) all the baseline [H 3 ]‐thymidine uptake, number of cells, and fibronectin production of mesangial cells can be partly suppressed by BQ123, but not by IRL1038; (3) the increment of Ang‐II‐enhanced number of cells can be partly suppressed by BQ123, but not by IRL1038; and (4) the increment of Ang‐II‐enhanced fibronectin production can be partly suppressed by both BQ123 and IRL1038. Our results indicate that Ang‐II is an active stimulant for the proliferation and fibronectin production of mesangial cells, and the effect is partly suppressed mainly by ET‐1 type A receptor antagonists.