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MiR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Meng, Li Cao, Haohao Wan, Chun-Hua Jiang, Lintao |
| Copyright Year | 2019 |
| Abstract | INTRODUCTION Sepsis-induced acute lung injury (ALI) is an inflammatory process involved with simultaneous production of inflammatory cytokines and chemokines. In this study, we investigated the regulatory role of miR-539-5p in sepsis-induced ALI using a mouse model of cecal ligation puncture (CLP) and an in vitro model of primary murine pulmonary microvascular endothelial cells (MPVECs). MATERIAL AND METHODS Adult male C57BL/6 mice were intravenously injected with or without miR-539-5p agomir or scrambled control one week before CLP operation. MPVECs were transfected with miR-539-5p mimics or control mimics, followed by lipopolysaccharide (LPS) stimulation. ROCK1 was predicted and confirmed as a direct target of miR-539-5p using dual-luciferase reporter assay. In rescue experiment, MPVECs were co-transfected with lentiviral vector expressing ROCK1 (or empty vector) and miR-539-5p mimics 24 h before LPS treatment. The transcriptional activity of caspase-3, the apoptosis ratio, the levels of miR-539-5p, interleukin-1β (IL-1b), interleukin-6 (IL-6), and ROCK1 were assessed. RESULTS Compared to sham group, mice following CLP showed pulmonary morphological abnormalities, elevated production of IL-1b and IL-6, and increased caspase-3 activity and apoptosis ratio in the lung. In MPVECs, LPS stimulation resulted in a significant induction of inflammatory cytokine levels and apoptosis compared to untreated cells. The overexpression of miR-539-5p in septic mice alleviated sepsis-induced pulmonaryinjury, apoptosis, and inflammation. MiR-539-5p also demonstrated anti-apoptotic and anti-inflammatory effect in LPS-treated MPVECs. The upregulation of ROCK1 in MPVECs recovered miR-539-5p-suppressed caspase-3 activity and proinflammatory cytokine production. CONCLUSION In conclusion, miR-539-5p alleviated sepsis-induced ALI via suppressing its downstream target ROCK1, suggesting a therapeutic potential of miR-539-5p for the management of sepsis-induced ALI. |
| File Format | PDF HTM / HTML |
| DOI | 10.5603/FHC.a2019.0019 |
| PubMed reference number | 31825519 |
| Journal | Medline |
| Alternate Webpage(s) | https://journals.viamedica.pl/folia_histochemica_cytobiologica/article/download/FHC.a2019.0019/49734 |
| Alternate Webpage(s) | https://doi.org/10.5603/FHC.a2019.0019 |
| Journal | Folia histochemica et cytobiologica |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
