https://scholars.lib.ntu.edu.tw/handle/123456789/635369
標題: | 5-methoxytryptophan: an arsenal against vascular injury and inflammation | 作者: | Wu, Kenneth K Kuo, Cheng-Chin Yet, Shaw-Fang CHII-MING LEE Liou, Jun-Yang |
關鍵字: | 5-methoxytryptophan; Chronic renal failure; Endothelial barrier function; Heart failure; Hydroxyindole O-methyltransferase; Intimal hyperplasia; Macrophage activation; Sepsis; Smooth muscle cell migration and proliferation; Tryptophan hydroxylase-1 | 公開日期: | 7-七月-2020 | 卷: | 27 | 期: | 1 | 起(迄)頁: | 79 | 來源出版物: | Journal of biomedical science | 摘要: | 5-methoxytryptophan (5-MTP) is an endothelial factor with anti-inflammatory properties. It is synthesized from L-tryptophan via two enzymatic steps: tryptophan hydroxylase-1 (TPH-1) and hydroxyindole O-methyltransferase. Lipopolysaccharide (LPS) and pro-inflammatory cytokines suppress endothelial 5-MTP production by inhibiting TPH-1 expression. 5-MTP protects endothelial barrier function and promotes endothelial repair, while it blocks vascular smooth muscle cell migration and proliferation by inhibiting p38 MAPK activation. 5-MTP controls macrophage transmigration and activation by inhibiting p38 MAPK and NF-κB activation. 5-MTP administration attenuates arterial intimal hyperplasia, defends against systemic inflammation and prevents renal fibrosis in relevant murine models. Serum 5-MTP level is depressed in human sepsis as well as in mice with sepsis-like disorder. It is reduced in chronic kidney disease and acute myocardial infarction in humans. The reported data suggest that serum 5-MTP may be a theranostic biomarker. In summary, 5-MTP represents a new class of tryptophan metabolite which defends against inflammation and inflammation-mediated tissue damage and fibrosis. It may be a valuable lead compound for developing new drugs to treat complex human inflammatory disorders. |
URI: | https://www.scopus.com/record/display.uri?eid=2-s2.0-85087711541&doi=10.1186%2fs12929-020-00671-w&origin=inward&txGid=603d91f8b9c48379edd154db999c21e1 https://scholars.lib.ntu.edu.tw/handle/123456789/635369 |
ISSN: | 10217770 | DOI: | 10.1186/s12929-020-00671-w |
顯示於: | 醫學系 |
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