| First Author | Zhao J | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 52 | Pages | 18638-18648 |
| PubMed ID | 33109608 | Mgi Jnum | J:300946 |
| Mgi Id | MGI:6490912 | Doi | 10.1074/jbc.RA120.014861 |
| Citation | Zhao J, et al. (2020) Transcription factor NF-kappaB promotes acute lung injury via microRNA-99b-mediated PRDM1 down-regulation. J Biol Chem 295(52):18638-18648 |
| abstractText | Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-kappaB [NF-kappaB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-kappaB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-kappaB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1beta, IL-6, and TNFalpha) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-kappaB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-kappaB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1. |
