Stable Expression of Hypoxia-Inducible Factor-1α in Human Renal Proximal Tubular Epithelial Cells Promotes Epithelial to Mesenchymal Transition

BackgroundLate kidney allograft dysfunction is becoming a significant problem and tubular atrophy and interstitial fibrosis are main causes. It was reported that hypoxia could induce epithelial—mesenchymal transition (EMT) in renal tubular epithelial cells (TECs), and hypoxia-inducible factor-1 (HIF-1) is one of the important regulators of cellular adaptive to hypoxia.MethodsIn this study, we used an HIF-1αΔODD–expressing adenovirus, which could stably and functionally express HIF-1α under normoxia conditions, and used a hypoxia/reoxygenation cell model to simulate ischemia/reperfusion (I/R) injury in vitro, to investigate the effect of HIF-1α on EMT-related gene expressions.ResultsOur results demonstrated that HIF-1α could significantly upregulate α-smooth muscle actin expression, and reduced the E-cadherin expression in HK-2 cells during I/R injury. Moreover, miR-21 expression had a positive correlation with HIF-1α in this process.ConclusionThese results suggest that HIF-1α may promote the EMT development through regulating fibrotic gene expression during I/R injury in human renal TECs, and miR-21 could be among the important regulatory pathways in the process.