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Downregulation of miR-96 suppresses the profibrogenic functions of cardiac fibroblasts induced by angiotensin II and attenuates atrial fibrosis by upregulating KLF13

Abstract

Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). MicroRNA-96 (miR-96) has been reported to be associated with pulmonary fibrosis and hepatic fibrosis. Nevertheless, the role of miR-96 in atrial fibrosis is still unclear. In our study, we showed that miR-96 is upregulated in human atrial tissues from AF patients and positively correlates with collagen I and collagen III levels. Knockdown of miR-96 reduced angiotensin II (Ang-II)-induced cardiac-fibroblast proliferation, migration, and collagen production, whereas ectopic expression of miR-96 yielded opposite results. Furthermore, we demonstrated that miR-96 represses KLF13 expression, subsequently promoting Ang-II-induced proliferation, migration, and collagen production in murine cardiac fibroblasts. Moreover, we observed that the knockdown of miR-96 attenuated the Ang-II-induced atrial fibrosis in a mouse model of AF. All the findings point to a potential target for the prevention or treatment of atrial fibrosis.

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Correspondence to Wei Song.

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The authors confirm that there are no conflicts of interest.

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All animal experiments were performed in accordance with the institutional guidelines from the Care and Use of Laboratory Animals of Shu Guang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine and were approved by the Institutional Animal Ethics Committee.

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Su, L., Yao, Y. & Song, W. Downregulation of miR-96 suppresses the profibrogenic functions of cardiac fibroblasts induced by angiotensin II and attenuates atrial fibrosis by upregulating KLF13. Human Cell (2020). https://doi.org/10.1007/s13577-020-00326-w

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Keywords

  • Atrial fibrillation
  • Atrial fibrosis
  • MicroR-96
  • KLF13