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. 2023 Sep;59(8):596-605.
doi: 10.1007/s11626-023-00812-z. Epub 2023 Oct 2.

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

Shuai An #  1 , Jingfei Shi #  2 , Jiang Huang  1 , Zheng Li  1 , Mingli Feng  3 , Guanglei Cao  4
Affiliations

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

Shuai An et al. In Vitro Cell Dev Biol Anim. 2023 Sep.

Abstract

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.

Keywords: HIF-1α; IGF2BP1; Peripheral nerve injury; SLC7A11; m6A.

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References

    1. An S, Shi J, Li Z, Feng M, Cao G (2022) The effects of acrylamide-mediated dorsal root ganglion neurons injury on ferroptosis. Hum Exp Toxico 41:9603271221129786 - DOI
    1. An S, Zhou M, Li Z, Feng M, Cao G, Lu S, Liu L (2018) Administration of CoCl2 improves functional recovery in a rat model of sciatic nerve transection injury. Int J Med Sci 15:1423–1432 - PubMed - PMC - DOI
    1. Bergmeister KD, Große-Hartlage L, Daeschler SC, Rhodius P, Böcker A, Beyersdorff M, Kern AO, Kneser U, Harhaus L (2020) Acute and long-term costs of 268 peripheral nerve injuries in the upper extremity. PLoS One 15:e0229530 - PubMed - PMC - DOI
    1. Berulava T, Buchholz E, Elerdashvili V, Pena T, Islam MR, Lbik D, Mohamed BA, Renner A, Von Lewinski D, Sacherer M, Bohnsack KE, Bohnsack MT, Jain G, Capece V, Cleve N, Burkhardt S, Hasenfuss G, Fischer A, Toischer K (2020) Changes in m6A RNA methylation contribute to heart failure progression by modulating translation. Eur J Heart Fail 22:54–66 - PubMed - DOI
    1. Chen X, Xiao J-W, Cao P, Zhang Y, Cai W-J, Song J-Y, Gao W-M, Li B (2021) Brain-derived neurotrophic factor protects against acrylamide-induced neuronal and synaptic injury via the TrkB-MAPK-Erk1/2 pathway. Neural Regen Res 16:150–157 - PubMed - DOI

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