Research Paper Volume 13, Issue 2 pp 2640—2654
MiR-16-5p suppresses myofibroblast activation in systemic sclerosis by inhibiting NOTCH signaling
- 1 Department of Rheumatology and Immunology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
- 2 Department of Respiratory Medicine, The affiliated Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
- 3 Department of Pharmacy, The Second Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, China
Received: September 3, 2020 Accepted: November 11, 2020 Published: December 19, 2020https://doi.org/10.18632/aging.202308
How to Cite
Copyright: © 2020 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Systemic sclerosis (SSc) is a prototypic fibrotic disease characterized by localized or diffuse skin thickening and fibrosis. Tissue fibrosis is driven by myofibroblasts, and factors affecting myofibroblast activation may also be involved in the development of SSc. In this study, we examined molecular mechanisms underlying SSc by focusing on myofibroblast activation processes. Bioinformatics analysis conducted to identify differentially expressed miRNAs (DEMs) and genes (DEGs) revealed that microRNA-16-5p (miR-16-5p) was downregulated and NOTCH2 was upregulated in SSc patients. In vitro experiments confirmed that miR-16-5p was able to bind directly to NOTCH2 and inhibit myofibroblast activation. Moreover, miR-16-5p-dependent inhibition of NOTCH2 decreased collagen and α-SMA expression. MiR-16-5p downregulation and NOTCH2 upregulation was also confirmed in vivo in SSc patients, and NOTCH2 activation promoted fibrosis progression in vitro. These results indicate that miR-16-5p suppresses myofibroblast activation by suppressing NOTCH signaling.