- 期刊
Endothelin-1 Antisense Oligonucleotide Suppresses the Proliferation of Glomerular Mesangial Cells Stimulated with Angiotensin-Ⅱ
內皮素－1反譯寡核苷酸抑制第二型血管收縮素所誘發之腎絲球間質細胞增生
摘要
反譯寡核苷酸（以下簡稱AON）最近被報告可能做為臨床治療用途。我們曾報告第二型血管收縮素（以下簡稱Ang-Ⅱ)，會刺激另一個更強的細胞激素，內皮素－1（以下簡稱ET-1）之產生，因此本研究之目的即探討ET-1 AON對Ang-Ⅱ所誘發之腎絲球間質細胞增生之影響。ET-1係以放射免疫分析法測定。研究結果(1)Ang-Ⅱ可誘發腎絲球問質細胞產製較多量ET-1(2)ET-1 AON可抑制腎絲球間質細胞ET-1之產量，而ET-1 sense及scramble寡核苷酸則沒有類似作用(3)Ang-Ⅱ可刺激腎絲球間質細胞增加thymidine攝取量，此增加可受ET-1 AON部分抑制，但ET-1 sense及scramble寡核苷酸則沒有類似作用。本研究結果顯示ET-1 AON可明顯抑制腎絲球間質細胞之ET-1產量及Ang-Ⅱ所誘發之細胞增生。
並列摘要
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.
延伸閱讀
- Chang, J. W., Lin, C. Y., & Yang, A. H. (2000). 甲基類固醇脈衝式療法合併環孢靈及血管收縮素II拮抗劑成功治療第一型原發性膜厚增生型腎絲球腎炎. Acta Nephrologica, 14(2), 71-74. https://www.airitilibrary.com/Article/Detail?DocID=10131671-200004-14-2-71-74-a
- Chen, H. C., Guh, J. Y., & Lai, Y. H. (2000). 微小變化症時腎絲球產製之內皮素－1在體內及體外研究均受到活性氧族之調節. Acta Nephrologica, 14(4), 254-254. https://www.airitilibrary.com/Article/Detail?DocID=10131671-200010-14-4-254-254-o
- 王錦鳳（2003）。血管收縮素II活化腎絲球體環間膜細胞磷脂醯肌醇3激酶之訊息傳遞路徑及HIF-1α 的累積〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714512937
- Cheng, C. Y. (2008). Celecoxib抑制腎小管細胞經壓力所導致之轉化生長因子b表現及細胞外間質之生成 [master's thesis, Taipei Medical University]. Airiti Library. https://doi.org/10.6831/TMU.2008.00101
- 朱培倫（2004）。第二型血管張力素第二型受器對醛固酮分泌和腎上腺細胞自毀的影響及機制之探討〔碩士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2004.01759