Hypoxia is a common intrauterine stressor, often resulting in intrauterine growth restriction and increased risk for cardiovascular disease later in life. The aim of this work was to test the hypothesis that microRNA-210 (miR-210) mediates the detrimental suppression of glucocorticoid receptor (GR) in response to hypoxia in fetal rat cardiomyocytes. Cardiomyocytes isolated from gestational day 21 Sprague Dawley fetal rats showed increased miR-210 levels and reduced GR abundance after exposure to ex vivo hypoxia (1% O2). In regard to mechanisms, the different contributions of hypoxia response elements (HREs) motifs in the regulation of miR-210 promoter activity and the miR-210-mediated repression of GR expression were determined in rat embryonic heart-derived myogenic cell line H9c2. Moreover, using a cell culturebased model of hypoxia-reoxygenation injury, we assessed the cytotoxic effects of GR suppression under hypoxic conditions. The results showed that hypoxia induced HIF-1a-dependent miR-210 production, as well as miR-210-mediated GR suppression, in cardiomyocytes. Furthermore, inhibition or knockdown of GR exacerbated cell death in response to hypoxia-reoxygenation injury. Altogether, the present study demonstrates that the HIF-1a-dependent miR-210-mediated suppression of GR in fetal rat cardiomyocytes increases cell death in response to hypoxia, providing novel evidence for a possible mechanistic link between fetal hypoxia and programming of ischemic-sensitive phenotype in the developing heart. Copyright: Martinez et al.
S.R., M., Q., M., C., D., X., M., & L., Z. (2017). MicroRNA-210 suppresses glucocorticoid receptor expression in response to hypoxia in fetal rat cardiomyocytes. Oncotarget, 8(46), 80249–80264. https://doi.org/10.18632/oncotarget.17801 LK - http://sfx.library.uu.nl/utrecht?sid=EMBASE&issn=19492553&id=doi:10.18632%2Foncotarget.17801&atitle=MicroRNA-210+suppresses+glucocorticoid+receptor+expression+in+response+to+hypoxia+in+fetal+rat+cardiomyocytes&stitle=Oncotarget&title=Oncotarget&volume=8&issue=46&spage=80249&epage=80264&aulast=Martinez&aufirst=Shannalee+R.&auinit=S.R.&aufull=Martinez+S.R.&coden=&isbn=&pages=80249-80264&date=2017&auinit1=S&auinitm=R.