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In this study, we show that miR-204 expression in PASMCs is down-regulated in both human and rodent PAH. miR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity. This study uncovers a new regulatory pathway involving miR-204 that is critical to the etiology of PAH and indicates that reestablishing miR-204 expression should be explored as a potential new therapy for this disease.<\/jats:p>","DOI":"10.1084\/jem.20101812","type":"journal-article","created":{"date-parts":[[2011,2,15]],"date-time":"2011-02-15T05:15:05Z","timestamp":1297746905000},"page":"535-548","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":485,"title":["Role for miR-204 in human pulmonary arterial hypertension"],"prefix":"10.1084","volume":"208","author":[{"given":"Audrey","family":"Courboulin","sequence":"first","affiliation":[{"name":"D\u00e9partement de m\u00e9decine, Facult\u00e9 de m\u00e9decine 1 , 2 , and 3"},{"name":"Centre de recherche en canc\u00e9rologie de l\u2019Universit\u00e9 Laval, H\u00f4tel-Dieu de Qu\u00e9bec 1 , 2 , and 3"},{"name":"Institut universitaire de cardiologie et de pneumologie de 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