期刊
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
卷 301, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.resp.2022.103891
关键词
Asthma; MiR-21; Poly (ADP-ribose) polymerase-1; Autophagy; Human airway smooth muscle cell; AMPK; mTOR signalling pathway
资金
- Jiangsu Province Social Development Project, China [BE2020651]
- Jiangsu Province 333 Talents Project, China [BRA2020015]
- Changzhou Sci & Tech Program, China [CE20205023]
This study found that miR-21 promotes cell proliferation and inhibits autophagy in HASM cells by downregulating PARP-1. MiR-21 inhibitor upregulates PARP-1, inhibits cell proliferation, promotes apoptosis, and may be mediated by the AMPK/mTOR signaling pathway.
Superfluous human airway smooth muscle (HASM) cell proliferation is an important pathological feature of airway remodelling in asthma. This study aimed to determine whether miR-21 is involved in the regulation of HASM cell survival. Overexpressed miR-21 inhibited HASM cell apoptosis and autophagy and promoted proliferation, whereas a miR-21 inhibitor exerted the opposite effects (P < 0.05). Overexpressed poly (ADP-ribose) polymerase-1 (PARP-1) promoted apoptosis and inhibited proliferation of HASM cells (P < 0.05). Dual-luciferase assays confirmed that miR-21 directly targeted poly (ADP-ribose) polymerase-1 (PARP-1) mRNA (P < 0.05). Silencing PARP-1 based on miR-21 downregulation mimicked the role of 3-methyladenine (3-MA), an autophagy inhibitor (P < 0.05). Overexpressed PARP-1 reversed the effects of miR-21 on HASM cells, somewhat dependently on PARP-1-induced enhanced autophagy, which we elucidated by 3-MA block (P < 0.05). MicroRNA-21 mimics reduced AMPK and increased mTOR signalling by downregulating PARP-1, and a miR-21 inhibitor exerted the opposite effects (P < 0.05). Collectively, miR-21 inhibitor could upregulate PARP-1 in HASM cells to promote autophagy and thus inhibit proliferation and promote apoptosis that might be mediated by the AMPK/ mTOR signalling pathway.
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