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HIF‑1α‑induced upregulation of m6A reader IGF2BP1 facilitates peripheral nerve injury recovery by enhancing SLC7A11 mRNA stabilization

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机构： [1]Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. [2]Cerebrovascular and Neuroscience Research Institute, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.

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关键词： Peripheral nerve injury HIF-1α IGF2BP1 m6A SLC7A11

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The recovery of peripheral nerve injury (PNI) is not ideal in clinic. Our previous study revealed that hypoxia treatment promoted PNI repair by inhibiting ferroptosis. The aim of this study was to investigate the underlying molecular mechanism of HIF-1α in hypoxia-PNI recovery. M6A dot blot was used to determine the total level of m6A modification. Besides, HIF-1α small interfering RNA (siRNA) or IGF2BP1 overexpression vector was transfected into dorsal root ganglion (DRG) neurons to alter the expression of HIF-1α and IGF2BP1. Subsequently, MeRIP-PCR analysis was applied to validate the m6A methylation level of SLC7A11. We demonstrated the hypoxia stimulated HIF-1α-dependent expression of IGF2BP1 and promoted the overall m6A methylation levels of DRG neurons. Overexpression of HIF-1α increased the expressions of neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF), which could be effectively reversed by siRNA knockdown of IGF2BP1. Moreover, upregulation of HIF-1α contributed to the m6A methylation level and mRNA stabilization of SLC7A11. This study revealed that the HIF-1α/IGF2BP1/SLC7A11 regulatory axis facilitated the recovery of injured DRG neurons. Our findings suggest a novel insight for the m6A methylation modification in PNI recovery.© 2023. The Society for In Vitro Biology.

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出版当年[2022]版：

大类 | 4 区生物学

小类 | 4 区发育生物学 4 区细胞生物学

最新[2023]版：

大类 | 4 区生物学

小类 | 4 区细胞生物学 4 区发育生物学

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出版当年[2021]版：

Q3 DEVELOPMENTAL BIOLOGY Q4 CELL BIOLOGY

最新[2023]版：

Q4 CELL BIOLOGY Q4 DEVELOPMENTAL BIOLOGY

影响因子： 1.5 最新[2023版] 1.8 最新五年平均 2.723 出版当年[2021版] 2.303 出版当年五年平均 2.416 出版前一年[2020版] 2.1 出版后一年[2022版]

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第一作者机构： [1]Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.

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