Effects of Endothelin (ET) Receptors Specific Antagonist and ET-1 Antisense Oligonucleotides on Mesangial Cell Proliferation and Matrix Production

• Main Authors: Hsu Yun-Ting, 許芸婷
• Other Authors: J-H Tsai
• Format: Others
• Language: en_US
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/73796037061578669710

碩士 === 高雄醫學院 === 生物化學研究所 === 87 === Renal ET-1 does play a role in the process of nephropathy. Treatment with a specific ETA receptor antagonist or an ETA/ETB antagonist prevented ectracellular matrix accumulation and glomerulosclerosis in some models of kidney injury, such as remnant kidney, immune complex, lupus nephritis and diabetic nephropathy et al.. So reduced effect of ET-1 could decrease or prevent the progression of nephropathy. In this study, we evaluated the effects of ET-1 antisense oligonucleotides and ET-1 receptor antagonist on biological functions of ET-1 in rat mesangial cells. ET-1 antisense oligonucleotides could effectively inhibit the synthesis and secretion of ET-1 from mesangial cells. And ET-1 antisense oligonucleotides could specificlally block the DNA synthesis induced by FCS and Ang-II(angiotensin-II, 10-7M). The mitogenic effects of ET-1 and Ang-II were blocked by antagonist of ETA receptor (BQ123) but not ETB (IRL1038). It demonstrated that ET-1 stimulated cell proliferation via ETA receptor and ET-1 may contribute to mitogenic effect of Ang-II. If we combine both effects of ET-1 antisense oligonucleotides and ET-1 antagonists it may get better result in lowering pathological effects of ET-1. These findings may offer a possible route for clinical treatment.