Endothelin-1 antisense oligonucleotide suppresses the proliferation of glomerular mesangial cells stimulated with angiotensin-II.
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.
Lee
Jia-Jung
JJ
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Shin
Shyi-Jang
SJ
Chiu
Yi-Wen
YW
Chen
Hung-Chun
HC
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
D019332:Endothelin-1; D016376:Oligonucleotides, Antisense; D000804:Angiotensin II; D013936:Thymidine