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N-methyladenosine (mA) Writer METTL3 Accelerates the Apoptosis of Vascular Endothelial Cells in High Glucose

Overview
Journal Heliyon
Specialty Social Sciences
Date 2023 Mar 6
PMID 36873555
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Abstract

Recent studies have shown that N-methyladenosine (mA) methylation, one of the most prevalent epigenetic modifications, is involved in diabetes mellitus. However, whether mA regulates diabetic vascular endothelium injury is still elusive. Present research aimed to investigate the regulation and mechanism of mA on vascular endothelium injury. Upregulation of METTL3 was observed in the high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs), following with the upregulation of mA methylation level. Functionally, METTL3 silencing repressed the apoptosis and recovered the proliferation of HUVECs disposed by HG. Moreover, HG exposure upregulated the expression of suppressor of cytokine signaling3 (SOCS3). Mechanistically, METTL3 targeted the mA site on SOCS3 mRNA, which positively regulated the mRNA stability of SOCS3. In conclusion, METTL3 silencing attenuated the HG-induced vascular endothelium cells injury via promoting SOCS3 stability. In conclusion, this research expands the understanding of mA on vasculopathy in diabetes mellitus and provides a potential strategy for the protection of vascular endothelial injury.

Citing Articles

METTL3-Mediated m6A Modification of ISG15 mRNA Regulates Doxorubicin-Induced Endothelial Cell Apoptosis.

Jian D, Li H, Wang C, Li F, Li R, Jin S J Cell Mol Med. 2025; 29(1):e70339.

PMID: 39789417 PMC: 11717669. DOI: 10.1111/jcmm.70339.

References
1.
Li H, Xiao W, He Y, Wen Z, Cheng S, Zhang Y . Novel Insights Into the Multifaceted Functions of RNA n-Methyladenosine Modification in Degenerative Musculoskeletal Diseases. Front Cell Dev Biol. 2022; 9:766020. PMC: 8743268. DOI: 10.3389/fcell.2021.766020. View

2.
Gao J, Fan J, Meng Z, Wang R, Liu C, Liu J . Nicotine aggravates vascular adiponectin resistance via ubiquitin-mediated adiponectin receptor degradation in diabetic Apolipoprotein E knockout mouse. Cell Death Dis. 2021; 12(6):508. PMC: 8131622. DOI: 10.1038/s41419-021-03772-y. View

3.
Li J, Duan H, Liu Y, Wang L, Zhou X . Biomaterial-Based Therapeutic Strategies for Obesity and Its Comorbidities. Pharmaceutics. 2022; 14(7). PMC: 9320151. DOI: 10.3390/pharmaceutics14071445. View

4.
Patel V, Chorawala M, Shah M, Shah K, Dave B, Shah M . Emerging Pathophysiological Mechanisms Linking Diabetes Mellitus and Alzheimer's Disease: An Old Wine in a New Bottle. J Alzheimers Dis Rep. 2022; 6(1):349-357. PMC: 9277673. DOI: 10.3233/ADR-220021. View

5.
Wang H, Hu X, Huang M, Liu J, Gu Y, Ma L . Mettl3-mediated mRNA mA methylation promotes dendritic cell activation. Nat Commun. 2019; 10(1):1898. PMC: 6478715. DOI: 10.1038/s41467-019-09903-6. View