| First Author | Wang T | Year | 2019 |
| Journal | Cell Cycle | Volume | 18 |
| Issue | 16 | Pages | 1893-1907 |
| PubMed ID | 31208297 | Mgi Jnum | J:295311 |
| Mgi Id | MGI:6455320 | Doi | 10.1080/15384101.2019.1632136 |
| Citation | Wang T, et al. (2019) Inhibition of miR-221 alleviates LPS-induced acute lung injury via inactivation of SOCS1/NF-kappaB signaling pathway. Cell Cycle 18(16):1893-1907 |
| abstractText | The role of inflammation response has been well documented in the development of acute lung injury (ALI). However, little is known about the functions of miRNAs in the regulation of inflammation in ALI. The aim of this study was to explore the effects of miRNAs in the regulation of inflammation in ALI and to elucidate the biomolecular mechanisms responsible for these effects. The expression profiles of miRNAs in lung tissues from lipopolysaccharide (LPS)-induced ALI mice model were analyzed using a microarray. It was observed that microRNA-221-3p (miR-221) was significantly increased in lung tissues in ALI mice. The inhibition of miR-221 attenuated lung injury including decreased lung W/D weight ratio and lung permeability and survival rates of ALI mice, as well as apoptosis, whereas its agomir-mediated upregulation exacerbated the lung injury. Concomitantly, miR-221 inhibition significantly reduced LPS-induced pulmonary inflammation, while LPS-induced pulmonary inflammation was aggravated by miR-221 upregulation. Of note, suppressor of cytokine signaling-1 (SOCS1), an effective suppressor of the NF-kappaB signaling pathway, was found to be a direct target of miR-221 in RAW264.7 cells. Overexpression of SOCS1 by pcDNA-SOCS1 plasmids markedly reversed the miR-221 inhibition-mediated inhibitory effects on inflammation and apoptosis in LPS-treated RAW264.7 cells. Finally, it was found that miR-221 inhibition suppressed LPS induced the activation of the NF-kappaB signaling pathway, as demonstrated by downregulation of phosphorylated-IkappaBalpha, p-p65 and upregulation of IkappaBalpha, whilst miR-221 overexpression had an opposite result in ALI mice. Our findings demonstrate that inhibition of miR-221 can alleviate LPS-induced inflammation via inactivation of SOCS1/NF-kappaB signaling pathway in ALI mice. |
