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DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis

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Abstract

Aim and objective

Regulation of microRNA gene expression by DNA methylation may represent a key mechanism to drive cardiac fibrosis progression. Cardiac fibroblast autophagy is the primary source of cardiac fibrosis, but the mechanisms underlying this process are incompletely understood. Here we found that DNMT3A suppression of the microRNA-200b (miR-200b) through pathway leads to cardiac fibroblast autophagy in cardiac fibrosis.

Methods

To understand the impact of DNMT3A on miR-200b at cardiac fibrosis, the rat cardiac fibrosis model was established via the abdominal aortic coarctation. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and cultured. The expression of DNMT3A, miR-200b, collagen I was measured by western blotting, immunohistochemistry and qRT-PCR. Gain- or loss-of-function approaches were used to manipulate DNMT3A and miR-200b.

Results

DNMT3A level was upregulated and negatively correlated with miR-200b expression in fibrosis tissues and cardiac fibroblast. We found that autophagy was activated by miR-200b inhibitor and inactivated by miR-200b mimic in the rat cardiac fibroblast. Knockdown of DNMT3A notably increased the expression of miR-200b.

Conclusions

Taken together, these findings indicate that DNMT3A regulation of miR-200b controls cardiac fibroblast autophagy during cardiac fibrosis and provide a basis for the development of therapies for cardiac fibrosis.

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Abbreviations

miR-200b:

MicroRNA-200b

ECM:

Extracellular matrix

CFs:

Cardiac fibroblasts

DNMT3A:

DNA methyltransferases 3A

H&E:

Hematoxylin-eosin

siRNA:

Small interfering RNA

AO:

Acridine orange

PVDF:

Polyvinylidene fluoride

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Acknowledgements

This work was supported by grants from National Nature Scientific Foundation of China (no. 81700212, no. 81570295) and Natural Science Foundation of Anhui Provincial Education Department (KJ2017A168) and Natural Science Foundation of Anhui Provincial (1808085MH231).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Fu Rong Road, Hefei, 230601, Anhui, China

    Xu-Dong Zhao, Run-He Qin, Sheng-Song Xu, Hui Tao & Kai-Hu Shi

  2. School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

    Hui Tao & Xuan-Sheng Ding

  3. Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China

    Jing-Jing Yang

  4. Department of Cardiothoracic Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China

    Kai-Hu Shi

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  1. Xu-Dong Zhao
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  2. Run-He Qin
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Correspondence to Hui Tao or Kai-Hu Shi.

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The author declares that there is no competing interest.

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Responsible Editor: John Di Battista.

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Zhao, XD., Qin, RH., Yang, JJ. et al. DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis. Inflamm. Res. 67, 681–690 (2018). https://doi.org/10.1007/s00011-018-1159-2

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  • DOI: https://doi.org/10.1007/s00011-018-1159-2

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