Abstract
MicroRNAs (miRNAs) are important regulators of many cellular processes, and the dysregulation of miRNAs is associated with various diseases. MiR-100-5p is revealed to be downregulated in gestational hypertension, while its underlying regulatory mechanism remains unclear. The pathological condition of gestational hypertension was mimicked by the hypoxia and reoxygenation (H/R) treatment to human placental microvascular endothelial cells (HPMECs). RT-qPCR and western blotting were conducted to detect the mRNA and protein expression of RNAs. HPMEC viability was assessed by CCK-8 assay. HPMEC angiogenesis was examined using tube formation assay. The concentrations of ANG-1 and ANG-2 in HPMECs were detected by ELISA. The binding relationship between miR-100-5p and homeodomain interacting protein kinase 2 (HIPK2) was investigated using luciferase reporter assay. MiR-100-5p was downregulated in HPMECs after H/R treatment. MiR-100-5p overexpression reversed the H/R-induced decrease in viability, angiogenesis of HPMECs. HIPK2 was targeted by miR-100-5p in HPMECs, and miR-100-5p negatively modulated HIPK2 expression at the mRNA and protein levels. MiR-100-5p activated the PI3K/AKT pathway by downregulating HIPK2. Rescue assays demonstrated that miR-100-5p promoted the viability and angiogenesis of H/R treated HPMECs by targeting HIPK2 to activate the PI3K/AKT pathway. MiR-100-5p overexpression inhibits the dysfunction of HPMECs under hypoxia and reoxygenation by downregulating HIPK2 to activate the PI3K/AKT pathway.
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Zheng, H., Sun, Y., Shu, X. et al. Overexpression of microRNA-100-5p attenuates the endothelial cell dysfunction by targeting HIPK2 under hypoxia and reoxygenation treatment. J Mol Histol 52, 1115–1125 (2021). https://doi.org/10.1007/s10735-021-10002-4
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DOI: https://doi.org/10.1007/s10735-021-10002-4