Abstract
Aim
The regulatory mechanism of m6A regulators in vascular endothelial function of type
2 diabetes mellitus (T2DM) remains largely unknown. We addressed this issue based
on the data retrieved Gene Expression Omnibus (GEO) database and experimental validations.
Methods
Expression of m6A methylation regulators was evaluated in T2DM samples of GSE76894
dataset and GSE156341 dataset. Further analysis of candidate m6A methylation regulators
was conducted in the thoracic aorta of db/db mice and high glucose (HG)-induced human
umbilical vein endothelial cells (HUVECs). Ectopic expression and depletion experiments
were conducted to detect effects of m6A methylation regulators on vascular endothelial
function in T2DM.
Results
It emerged that three m6A methylation regulators (HNRNPC, RBM15B, and ZC3H13) were
highly expressed in T2DM, which were related to vascular EC function, showing diagnostic
values for T2DM. HNRNPC expression in the thoracic aorta of db/db mice was higher
than that in heterozygous db mice, and HNRNPC expression in HG-induced HUVECs was
upregulated when compared with normal glucose-exposed HUVECs. Furthermore, HNRNPC
activated PSEN1-dependent Notch pathway to induce eNOS inactivation and NO production
decrease, thereby causing vascular endothelial dysfunction in T2DM.
Conclusions
HNRNPC impaired vascular endothelial function to enhance the development of vascular
complications in T2DM through PSEN1-mediated Notch signaling pathway.
Keywords
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Article info
Publication history
Accepted:
January 16,
2023
Received in revised form:
December 26,
2022
Received:
July 31,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Published by Elsevier B.V.
