{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:22:28Z","timestamp":1773307348125,"version":"3.50.1"},"reference-count":34,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81230003"],"award-info":[{"award-number":["81230003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The ministry of Education of China","award":["20110071130009"],"award-info":[{"award-number":["20110071130009"]}]},{"name":"Shanghai Pujiang Program","award":["15PJ1400700"],"award-info":[{"award-number":["15PJ1400700"]}]},{"name":"Research center on Aging and Medicine, Fudan University","award":["13dz2260700"],"award-info":[{"award-number":["13dz2260700"]}]},{"name":"Key Laboratory program of the Education Commission of Shanghai Mulnicipality","award":["ZDSYS14005"],"award-info":[{"award-number":["ZDSYS14005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2016,2,15]]},"abstract":"<jats:p> We previously found hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) to be a new proangiogenic factor. However, the mechanisms underlying the cardiovascular effect of this small gas molecule remain largely unknown. The aim of the present study was to identify the essential microRNAs (miRNAs) involved in the transduction of H<jats:sub>2<\/jats:sub>S signals in vascular endothelial cells (ECs). The expression of miR-640 and its signaling elements, vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia inducible factor 1-\u03b1 (HIF1A), and mammalian target of rapamycin (mTOR), was measured using quantitative PCR and Western blotting. Overexpression and inhibition of miR-640 were performed to clarify their roles in mediating the effect of H<jats:sub>2<\/jats:sub>S. In addition, knockdown of VEGFR2, HIF1A, and mTOR was performed using siRNAs, dominant negative mutants, or inhibitors to examine their roles in the transduction of the H<jats:sub>2<\/jats:sub>S signals. miR-640 levels decreased in vascular ECs that were treated with H<jats:sub>2<\/jats:sub>S, whereas overexpression of miR-640 blunted the proangiogenic effect of H<jats:sub>2<\/jats:sub>S. Knockdown of either VEGFR2 or mTOR blunted the downregulation of miR-640 and the proangiogenic effect induced by H<jats:sub>2<\/jats:sub>S. In addition, miR-640 bound to the 3\u2032-UTR of HIF1A mRNA and then inhibited the expression of HIF1A. The inhibition could be recovered by treating cells with H<jats:sub>2<\/jats:sub>S. Thus we concluded that miR-640 plays a pivotal role in mediating the proangiogenic effect of H<jats:sub>2<\/jats:sub>S; H<jats:sub>2<\/jats:sub>S acts through downregulation of the expression of miR-640 and increasing the levels of HIF1A through the VEGFR2-mTOR pathway. <\/jats:p>","DOI":"10.1152\/ajpcell.00230.2015","type":"journal-article","created":{"date-parts":[[2015,11,26]],"date-time":"2015-11-26T04:00:00Z","timestamp":1448510400000},"page":"C305-C317","source":"Crossref","is-referenced-by-count":56,"title":["Hydrogen sulfide promotes angiogenesis by downregulating miR-640 via the VEGFR2\/mTOR pathway"],"prefix":"10.1152","volume":"310","author":[{"given":"Yu","family":"Zhou","sequence":"first","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai-Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"},{"name":"Department of Physiology, Hainan Medical College, Haikou, Hainan, China; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Long","family":"Xue","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Dong","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen-Fen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei-Bei","family":"Tao","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Chun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2183"},{"key":"B2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ceb.2014.12.001","volume":"33","author":"Albert V","year":"2014","journal-title":"Curr Opin Cell Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00084.2014"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1042\/BST0371193"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.05.026"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-0993-5"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67700-8"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5304"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.07.010"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.50.32253"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113305"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1110003"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.7748\/ns.19.43.59.s55"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5667"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3570-2"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00051"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.153916"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-216"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2305"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.05.012"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908047106"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.08.007"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.4.1474"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.5909"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000265065.26744.17"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804597105"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4565"},{"key":"B28","first-page":"129","volume":"64","author":"Tao BB","year":"2012","journal-title":"Sheng Li Xue Bao"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn156"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-229211"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2945"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-363457"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.8.765"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3114"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00230.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T16:15:10Z","timestamp":1718640910000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00230.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,15]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,2,15]]}},"alternative-id":["10.1152\/ajpcell.00230.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00230.2015","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,15]]}}}