Endothelin-1 Antisense Oligonucleotide Suppresses the Proliferation of Glomerular Mesangial Cells Stimulated with Angiotensin-II

Kaohsiung Journal of Medical Sciences

Shyi-Jang Shin¹  Hung-Chun Chen²  Yi-Wen Chiu²  Jia-Jung Lee² 

[1] Division of Endocrinology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;

关键词: angiotensin-II;    antisense oligonucleotide;    endothelin-1;    mesangial cell;   

DOI  :  10.1016/S1607-551X(09)70393-6

来源: DOAJ

【 摘 要 】

Antisense oligonucleotide (AON) has been applied to modern molecular pharmacology. We have previously demonstrated that angiotensin-II (Ang-II) is an active stimulator of endothelin-1 (ET-1) production in glomerular mesangial cells. This study was designed to investigate the specific effect of ET-1 AON on inducing proliferation of cultured rat mesangial cells stimulated with Ang-II. ET-1 was measured by radioimmunoassays. The results were: (1) Ang-II enhanced ET-1 production of mesangial cells; (2) ET-1 production of mesangial cells was significantly suppressed by ET-1 AON, and this production was not affected by either ET-1 sense or scramble oligonucleotide in different concentrations; (3) Ang-II increased [3H]-thymidine uptake of mesangial cells, which was suppressed to 25% by ET-1 AON but not by ET-1 sense or scramble oligonucleotide. Our results indicate that ET-1 AON effectively suppresses the ET-1 production and the Ang-II-stimulated proliferation of mesangial cells, and therefore may offer treatment for proliferative glomerulonephritis.

【 授权许可】

Unknown