The Roles of METTL3 on Autophagy and Proliferation of Vascular Smooth Muscle Cells Are Mediated by MTOR Rather Than by CDK1

Overview

Journal Cell Div

Publisher Biomed Central

Date 2023 Aug 9

PMID 37559091

Authors

Hanshen Luo

Xingliang Wu

Bo Huo

Liyuan Liu

Ding-Sheng Jiang

Xin Yi

Affiliations

Soon will be listed here.

Abstract

Background: Aberrant proliferation of vascular smooth muscle cells (VSMCs) is the cause of neointima formation followed by vascular injury. Autophagy is involved in this pathological process, but its function is controversial. Recently, we found that methyltransferase like 3 (METTL3) inhibited VSMC proliferation by activating autophagosome formation. Moreover, we also demonstrated that METTL3 reduced the levels of phosphorylated mammalian target of rapamycin (p-mTOR) and cyclin dependent kinase 1 (p-CDK1/CDC2), which were critical for autophagy and proliferation regulation. However, whether mTOR and CDK1 mediated the function of METTL3 on autophagy and proliferation in VSMCs remains unknown.

Results: We showed that the activator of mTOR, MHY1485 largely reversed the effects of METTL3 overexpression on VSMC autophagy and proliferation. Rapamycin, the inhibitor of mTOR, obviously nullified the pro-proliferation effects of METTL3 knockdown by activating autophagy in VSMCs. Unexpectedly, mTOR did not contribute to the impacts of METTL3 on migration and phenotypic switching of VSMCs. On the other hand, by knockdown of CDK1 in VSMC with METTL3 deficiency, we demonstrated that CDK1 was involved in METTL3-regulated proliferation of VSMCs, but this effect was not mediated by autophagy.

Conclusions: We concluded that mTOR but not CDK1 mediated the role of METTL3 on VSMC proliferation and autophagy.

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