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. 2021 Apr 16;10(4):919. doi: 10.3390/cells10040919

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Summary of the central role for miRNA-145 in influencing SV-SMC DNA damage, proliferation and senescence. DNA damage upregulates expression of miRNA-145 in addition to inducing cell cycle arrest (p21 and p53 phosphorylation), upregulating apical kinase expression (ATR, ATM, DNA-PK) and cellular senescence (IL-1α, Lamin B1 and SA β-gal. miRNA-145 reinforces DDR by also upregulating ATR expression, triggering intracellular kinase cascades (IκB, p38α, ERK) and inducing components of SASP (MCP-1, IL-6, IL-8). This induction of senescence and SASP inflicts a paracrine bystander effect on neighbouring cells through chronic activation of Akt and p38α, which can block cellular proliferation and perpetuate the T2DM-SMC phenotype.