Mettl14介导的m6A修饰对改善心肌梗死的分子机制

doi:10.3969/j.issn.1006-5725.2023.21.011

Abstract

Abstract:

Objective To investigate the biological role of methyltransferase-like 14 （METTL14）-mediated m6A modification in myocardial infarction （MI）. Methods A total of 40 mice were randomly divided into 4 groups： Sham+AAV9-NC group （n = 10）， Sham+AAV9-METTL14 group （n = 10）， MI+AAV9-NC group （n = 10） and MI+AAV9-METTL14 group （n = 10）. Mice in each group were injected with AAV9-METTL14 or AAV9-NC through the tail vein one week before MI induction. Cardiac function was measured non-invasively by transthoracic echocardiography， and microvascular injury were measured by immunofluorescence. CMECs were isolated from mouse myocardial tissue， and the cells were treated with oxygen-glucose deprivation （OGD）. Results METTL14 was downregulated in MI mouse heart tissue as well as in OGD-treated CMECs. Compared with the Sham+AAV9-NC group， the expression of VE-cadherin was significantly down-regulated （P < 0.05）， ROS levels increased significantly （P < 0.05） in the MI+AAV9-NC group. MI+AAV9-METTL14 suppressed these changes and enhanced cardiac function in mice. Compared with the NC group， a significant increase in mitochondrial ROS levels was observed in the OGD group （P < 0.05）. Knockdown of METTL14 in CMECs exacerbated ROS levels （P < 0.05）， and the addition of USP48 overexpression plasmid reversed these changes （P < 0.05）. Conclusion METTL14 was lowly expressed in MI and mediates mitochondrial dysfunction in CMECs by increasing the m6A modification level of USP48 in CMECs to reduce its stability.

Key words: methyltransferase-like 14, N6-methyladenosine, myocardial infarction, ubiquitin-specific peptidase 48

CLC Number:

Xuebin ZHENG,Sha SHA,Huiqiong YANG,Lian LIU. Molecular mechanism of Mettl14 mediated m6A modification in improving myocardial infarction[J]. The Journal of Practical Medicine, 2023, 39(21): 2754-2760.

Figures/Tables 6

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References 22

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参数	Sham+AAV9-NC组	Sham+AAV9-METTL14组	MI +AAV9-NC组	MI+AAV9-METTL14组	F值	P值
BW（g）	26.0 ± 1.0	26.1 ± 0.8	25.9 ± 0.7	25.9 ± 0.9	0.89	0.632
HW（mg）	156.4 ± 7.8	154.2 ± 8.3	237.6 ± 1.2^*	186.4 ± 9.6^#	28.50	< 0.001
HW/BW（mg/g）	6.04 ± 0.33	5.94 ± 0.58	9.27 ± 0.75^*	7.15 ± 0.66^#	8.24	< 0.001
HR（次/min）	451.7 ± 12.5	462.2 ± 14.1	477.4 ± 18.1	465.3 ± 17.4	1.75	0.315
LVDd（mm）	3.25 ± 0.14	3.31 ± 0.12	3.96 ± 0.16^*	3.57 ± 0.13^#	7.55	< 0.001
LVDs（mm）	2.24 ± 0.09	2.20 ± 0.11	3.15 ± 0.18^*	2.56 ± 0.13^#	20.22	< 0.001
IVS（mm）	0.82 ± 0.03	0.81 ± 0.02	0.70 ± 0.03^*	0.78 ± 0.04^#	10.77	< 0.001
PW（mm）	0.77 ± 0.05	0.76 ± 0.04	0.79 ± 0.03	0.78 ± 0.02	1.20	0.426
FS（%）	32.7 ± 1.5	33.1 ± 1.2	21.3 ± 2.3^*	29.4 ± 2.1^#	17.94	< 0.001
EF（%）	61.3 ± 2.7	62.1 ± 2.4	44.6 ± 4.8^*	58.2 ± 4.5^#	14.65	< 0.001

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Molecular mechanism of Mettl14 mediated m6A modification in improving myocardial infarction

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