THE LNCRNA, H19 MEDIATES THE PROTECTIVE EFFECT OF HYPOXIA POSTCONDITIONING AGAINST HYPOXIA-REOXYGENATION INJURY TO SENESCENT CARDIOMYOCYTES BY TARGETING MICRORNA-29B-3P
THE LNCRNA, H19 MEDIATES THE PROTECTIVE EFFECT OF HYPOXIA POSTCONDITIONING AGAINST HYPOXIA-REOXYGENATION INJURY TO SENESCENT CARDIOMYOCYTES BY TARGETING MICRORNA-29B-3P
复制标题
LNCRNA H19 通过靶向 MICRORNA-29B-3P 介导缺氧后处理对衰老心肌细胞的缺氧-复氧损伤的保护作用
DOI：
10.1097/shk.0000000000001213
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发表时间：
2019
期刊：
影响因子：
3.1
通讯作者：
Li Hao
中科院分区：
文献类型：
--
作者：
Zhang Xuan;Cheng Long;Xu Longhe;Zhang Yunliang;Yang Yitian;Fu Qiang;Mi Weidong;Li Hao
背景：缺血后适应（Ischemic postconditioning, I/Post）是一种内源性保护机制，可减轻缺血再灌注（ischemia-reperfusion, I/R）损伤。I/Post是否能防止老化心脏的I/R损伤仍存在争议。长链非编码RNA H19保护H9c2细胞免受缺氧诱导的损伤。本研究旨在阐明H19在衰老心肌细胞缺氧后适应（H/Post）中的作用。方法：采用衰老相关β-半乳糖苷酶染色法观察d -半乳糖对新生大鼠心肌细胞衰老的影响。通过细胞活力和凋亡检测评估缺氧损伤。实时聚合酶链反应检测缺氧复氧前后（H/R）和H/Post的H19表达。通过生物信息学分析预测mir -29b-3p在H19和细胞凋亡抑制蛋白1 （cIAP1）中的结合位点，并通过荧光素酶测定验证相互作用。观察H/Post后H19、miR-29b-3p和cIAP1表达改变对衰老心肌细胞活力和凋亡的影响。结果：H/Post对正常心肌细胞H/R损伤有抑制作用，对衰老心肌细胞H/R损伤无抑制作用。与正常心肌细胞相比，衰老心肌细胞H/Post后H19表达明显下调。衰老心肌细胞中小干扰rna介导的H19敲低增加H/后诱导损伤。miR-29b-3p受到H19的调控，导致更大的损伤。miR-29b-3p直接靶向cIAP1的3 ' -非翻译区，抑制其表达。此外，在H/Post后，cIAP1的敲低会损伤衰老的心肌细胞。结论：这些发现提示H19通过抑制miR-29b-3p的表达，介导H/Post对H/ r诱导的衰老心肌细胞损伤的抗凋亡作用。
Background:Ischemic postconditioning (I/Post) is an endogenous protection mechanism that reduces injury induced by ischemia-reperfusion (I/R). It remains controversial whether I/Post protects against I/R injury to the aging heart. The long non-coding RNA, H19 protects H9c2 cells against hypoxia-induced injury. This study aimed to elucidate the role of H19 in the hypoxic postconditioning (H/Post) of aged cardiomyocytes.Methods:Senescence induced by D-galactose in primary cardiomyocytes from neonatal Sprague–Dawley rats was measured by senescence-associated β-galactosidase staining. Hypoxic injury was evaluated by cell viability and apoptosis assays. H19 expression before and after hypoxia-reoxygenation (H/R) and H/Post was evaluated by real-time polymerase chain reactions. miR-29b-3p-binding sites in H19 and the cellular inhibitor of apoptosis protein 1 (cIAP1) were predicted by bioinformatics analysis, and interaction was verified by luciferase assay. The effects of altered H19, miR-29b-3p, and cIAP1 expression on the viability and apoptosis of senescent cardiomyocytes following H/Post were determined.Results:H/Post prevented H/R injury in normal but not senescent cardiomyocytes. H19 expression was remarkably down-regulated after H/Post in senescent compared with normal cardiomyocytes. Small interfering RNA-mediated knockdown of H19 in senescent cardiomyocytes increased H/Post-induced injury. miR-29b-3p was regulated by H19 and led to a greater injury. miR-29b-3p directly targeted the 3′-untranslated region of cIAP1 and suppressed its expression. Furthermore, knockdown of cIAP1 damaged senescent cardiomyocytes following H/Post.Conclusions:These findings suggest that H19 mediated the antiapoptotic effect of H/Post against H/R-induced injury to aged cardiomyocytes by inhibiting miR-29b-3p expression.