Role of m6A RNA methylation modification in necrotic apoptosis in a rat model of brain injury

doi:10.12307/2023.187

Abstract

Abstract: BACKGROUND: Mammalian central nervous system injury is dependent on the regulation of N6-methyladenosine (m6A) and is closely associated with necrotic apoptosis. At present, the relationship between m6A RNA methylation modification and necrotic apoptosis in rat models of traumatic brain injury has not been studied.
OBJECTION: To study the relationship between m6A RNA methylation and necrotic apoptosis in a rabbit brain injury model and to provide experimental basis for the molecular mechanism of occurrence, development and prognosis of necrotic apoptosis following craniocerebral injury.
METHODS: A total of 30 SPF male Sprague-Dawley rats were selected and randomized into sham operation group (n=10), traumatic brain injury group (n=10), and signal transducer and activator of transcription 1 (STAT1) inhibitor (NSC118218) group (n=10). The brain injury model was established using the modified Feeney method in the latter two groups, while the dura mater in the sham operation group was only exposed without striking. The levels of inflammatory factors, tumor necrosis factor ɑ, interleukin-6, interleukin-1β, interleukin-10, and high mobility group box 1 in the cerebral cortex of rats and brain water content were detected at 6 hours after brain injury. At the same time, the methylation level of total m6A RNA and the mRNA and protein expression levels of YTH domain family protein family 2 (YTHDF2), JAK1 and STAT1 were detected.
RESULTS AND CONCLUSION: The levels of inflammatory factors, brain water content, and the expression of JAK1 and STAT1 in the traumatic brain injury group and NSC118218 group were significantly higher than those in sham operation group, while the proportion of m6A RNA methylation and the expression level of YTHDF2 were significantly lower than those in the sham operation group (P < 0.05). The levels of inflammatory factors, brain water content, and the mRNA and protein expressions of JAK1 and STAT1 in the NSC118218 group were significantly lower than those in the traumatic brain injury group, while the proportion of m6A RNA methylation and the expression level of YTHDF2 were significantly increased (P < 0.05). These findings indicate that the proportion of m6A RNA methylation and YTHDF2 expression decrease after brain injury, which activates the JAK/STAT signaling pathway, increases the expression of JAK1 and STAT1, and thus promotes necrotic apoptosis in cells.

Key words: traumatic brain injury, m6A RNA methylation, necrotic apoptosis, JAK/STAT, animal model

CLC Number:

Lin Shukai, Liu Zhonghai, Liu Zhen, Cai Jincheng, Wei Ruting. Role of m6A RNA methylation modification in necrotic apoptosis in a rat model of brain injury[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(20): 3167-3172.

Figures/Tables 6

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