Startseite Lebenswissenschaften M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
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M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus

  • Bao-fu Zhang , Zi-heng Wu , Jie Deng , Hao-jie Jin , Wei-biao Chen , Sai Zhang , Xiu-jie Liu , Wan-tie Wang EMAIL logo und Xiang-tao Zheng EMAIL logo
Veröffentlicht/Copyright: 7. Dezember 2021
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 403 Heft 3

Abstract

Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m6A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m6A methylation modification regulatory mechanism. In this study, m6A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m6A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m6A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m6A methylation modified mRNA. In vivo studies confirmed that the elevated m6A modification level of SM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m6A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.

Keywords: intimal hyperplasia; N6-methyladenosine (m6A); Type 2 diabetes mellitus (T2DM); vascular smooth muscle cells (VSMCs)
Corresponding authors: Wan-tie Wang, Institute of Ischemia-Reperfusion Injury, Wenzhou Medical University, Central North Road, Chashan Advanced Education Park, Ouhai District, Wenzhou, Zhejiang 325035, China, E-mail: ; and Xiang-tao Zheng, Department of Vascular Surgery, The Second Affiliated Hospital of Wenzhou Medical University, No. 109, Xueyuan West Road, Wenzhou 325015, China, E-mail:
Bao-fu Zhang and Zi-heng Wu contributed equally to this work.

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81770409

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the National Natural Science Foundation of China (No. 81770409).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2021-06-15
Accepted: 2021-11-18
Published Online: 2021-12-07
Published in Print: 2022-02-23

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Research Articles
  3. Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
  4. Effect of myeloperoxidase oxidation and N-homocysteinylation of high-density lipoprotein on endothelial repair function
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  7. Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
  8. M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
  9. Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches
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https://doi.org/10.1515/hsz-2021-0296
Schlagwörter für diesen Artikel
intimal hyperplasia; N6-methyladenosine (m6A); Type 2 diabetes mellitus (T2DM); vascular smooth muscle cells (VSMCs)

Artikel in diesem Heft

  1. Frontmatter
  2. Research Articles
  3. Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
  4. Effect of myeloperoxidase oxidation and N-homocysteinylation of high-density lipoprotein on endothelial repair function
  5. High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis
  6. Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells
  7. Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
  8. M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
  9. Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches
  10. Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells
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