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• W2321933135 abstract "Abstract Aim Upregulation of miR‐21 in renal ischaemic preconditioning (IPC) was associated with increased hypoxia inducible factor (HIF)‐1α expression. Hypoxic induction of HIF‐1α is mediated by inhibition of prolyl hydroxylase domain protein 2 (PHD2) .We hypothesized that miR‐21 regulated HIF‐1α by targeting PHD2 in the renal IPC. Methods Luciferase reporter assay examined if miR‐21 target the 3'‐untranslated region of PHD2. In vitro, human proximal tubular cell line (HK‐2) was incubated in hypoxia or hypoxia/ reoxygenation condition. Kidneys of Mice were respectively subjected to ischaemia/reperfusion injury (IRI) and IPC. Locked nucleic acid (LNA) modified anti‐miR‐21 was used to knockdown miR‐21. Serum creatinine and histological changes estimated the renal injury. Levels of HIF‐1α, PHD2, VEGF and miR‐21 were examined by western blot or real‐time PCR. Result miR‐21 targeting of PHD2 was confirmed by 3'‐untranslated region reporter assay. miR‐21 was significantly upregulated by hypoxia/reoxygenation in HK‐2 cell, while PHD2 protein level decreased significantly. LNA anti‐miR‐21 significantly repressed miR‐21 levels and increased the abundance of PHD2. In vivo, IPC upregulated miR‐21 expression 24 h after the second ischaemia, while PHD2 expression decreased significantly with upregulation of HIF‐1α protein and VEGF mRNA. MiR‐21 induced by delayed IPC was effectively inhibited by the LNA anti‐miR‐21. With downregulation of miR‐21, the protection of delayed IPC was attenuated and PHD2 protein was increased. Furthermore, upregulation of HIF‐1α and VEGF were abolished after the LNA anti‐miR‐21 treatment. Conclusion miR‐21 could protect kidney against IRI via HIF‐1α by inhibiting its target PHD2.The study suggested a new relationship between miR‐21 and HIF‐1α." @default.
• W2321933135 created "2016-06-24" @default.
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• W2321933135 date "2017-04-04" @default.
• W2321933135 modified "2023-10-04" @default.
• W2321933135 title "miR-21 contributes to renal protection by targeting prolyl hydroxylase domain protein 2 in delayed ischaemic preconditioning" @default.
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• W2321933135 doi "https://doi.org/10.1111/nep.12787" @default.
• W2321933135 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27030384" @default.
• W2321933135 hasPublicationYear "2017" @default.
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