Expression profile of miRNA in chronic kidney disease and identification of miRNA regulating hypoxia and endoplasmic reticulum stress signals

为了探讨microRNA(MiRNA)在慢性肾脏疾病(CKD)中的病理生理功能，我们对缺氧诱导的氧化应激源内质网(ER)应激所致的人肾小管上皮细胞(HK-2)进行了miRNA芯片分析和功能丧失/恢复分析。结果表明：1)缺氧诱导的氧化应激或内质网应激显著降低miR-205的表达，并与细胞对应激的敏感性有关；2)降解缺氧和内质网应激信号转录因子(HIF、ATF4)的Phd1是miR-205的靶标；3)miR-205的下调通过上调Phd1来抑制HIF/ATF4下游基因的表达。MIR-205可能参与了肾小管内环境的稳定。

To assess the pathophysiological function of microRNA (miRNA) inchronic kidney disease (CKD), we performed the miRNA microarray analysis and the loss/gainfunction assay in human tubular cells (HK-2) expose to hypoxia-induced oxidative stressor endoplasmic reticulum (ER) stress. The results demonstrated that 1) miR-205 expressionwas significantly decreased by hypoxia-induced oxidative stress or ER stress and wasassociated with cellular sensitivity to the stresses, 2) PHD1, which degradestranscription factors (HIF, ATF4) of hypoxia and ER stress signals, is a target for miR-205,3) decreased miR-205 suppressed the expression of HIF/ATF4 downstream genes, anti-oxidantenzymes, via upregulation of PHD1. miR-205 might contribute to tubular homeostasis.