Together, our study provided the first evidence that MALAT1 knockdown could suppress inflammatory response by up-regulating miR-146a in LPS-induced ALI, which provided a potential therapeutic target for the treatment of ALI.
We identified a branch of the XIST/miR-137/Notch-1 pathway that regulates proliferation and TGF-β1-induced EMT in NSCLC, which could be involved in NSCLC progression.
Activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome received substantial attention recently in inflammatory diseases. Macrophages contribute to allergic inflammation in asthma. The present study was aimed to investigate the effect of NLRP3 inflammasome on the polarization of macrophages. We utilized human primary monocytes and monocyte-derived macrophages to study the expression of NLRP3 inflammasome components (NLRP3, apoptosis-associated specklike protein, and caspase-1) and its downstream cytokine interleukin-1β (IL-1β). By gain- or loss-of-function assays, we next explored the effects of NLRP3 inflammasome on M1/M2 polarization and secretion of IL-4, interferon-γ, tumor necrosis factor-α, and IL-1β. The results showed increased numbers of M2 cells in asthma. And NLRP3 inflammasome was activated and involved in the inflammation of asthma. Furthermore, silence of NLRP3 down-regulated IL-4 secretion and up-regulated M1/M2. In contrast, overexpression of NLRP3 increased IL-4 and decreased M1/M2. As expected, IL-4 was involved in NLRP3-mediated down-regulation of Ml/M2 ratio. Moreover, NLRP3 interacted with IRF4 and was required for optimal IRF4-dependent IL-4 transcription. Subsequently, deficiency of NLRP3 in ovalbumin-induced allergic asthmatic mice impaired lung inflammation and up-regulated M1/M2, and diminished IL-4 in bronchoalveolar lavage fluid. Collectively, we demonstrated here that activation of NLRP3 was engaged in the promotion of asthma. NLRP3, but not the inflammasome adaptor ASC or caspase-1, promoted the polarization of M2 macrophages through up-regulating the expression of IL-4, thereby contributing to its regulation of asthma.
Long noncoding RNAs (lncRNAs) are involved in various human diseases. Recently, H19 was reported to be upregulated in fibrotic rat lung and play a stimulative role in bleomycin (BLM)-induced pulmonary fibrosis in mice. However, its expression in human fibrotic lung tissues and mechanism of action remain unclear. Here, our observations showed that H19 expression was significantly upregulated and that of microRNA 140 (miR-140) was markedly reduced in pulmonary fibrotic tissues from idiopathic pulmonary fibrosis (IPF) patients and transforming growth factor β1 (TGF-β1)-induced HBE and A549 cells. Moreover, the expression of H19 was negatively correlated with the expression of miR-140 in IPF tissues. H19 knockdown attenuated TGF-β1-induced pulmonary fibrosis in vitro. Furthermore, animal experiments showed that H19 knockdown attenuated BLM-induced pulmonary fibrosis in mice. The study of molecular mechanisms showed that H19 functioned via reduction of miR-140 expression by binding to miR-140. The increase of miR-140 inhibited TGF-β1-induced pulmonary fibrosis, and H19 upregulation diminished the inhibitory effects of miR-140 on TGF-β1-induced pulmonary fibrosis, which was involved in the TGF-β/Smad3 pathway. Taken together, our findings showed that H19 knockdown attenuated pulmonary fibrosis via the regulatory network of lncRNA H19–miR-140–TGF-β/Smad3 signaling, and H19 and miR-140 might represent therapeutic targets and early diagnostic and prognostic biomarkers for patients with pulmonary fibrosis.
Injury to airway smooth muscle (ASM) cells hallmarks the pathological progression of asthma, a chronic inflammatory airway disease. MicroRNAs (miRNAs) play essential roles in the development of asthma as well as airway remodeling. Here we studied the involvement of miRNAs in the regulation of autophagic survival of ASM cells and airway disorder. We analyzed autophagy-associated factors LC3 and Beclin-1 by RT-qPCR and protein blotting in purified airway smooth muscle cells from ovalbumin (OVA)-induced asthmatic mice. The biological activity of miRNA targeting Beclin-1 was explored by bioinformatics method and confirmed in a dual luciferase reporter assay. Loss of function experiment was performed via transplantation of miRNA in OVA-induced asthmatic mice. We detected high autophagy levels in ASM cells, which appeared to result from augmentation of Beclin-1 protein, rather than Beclin-1 mRNA, suggesting presence of post-transcriptional control of Beclin-1. Next, miR-384 was figured out to be a Belcin-1-targeting miRNA, which significantly decreased after OVA treatment. Mechanistically, binding of miR-384 to 3’-UTR of Beclin-1 mRNA potently suppressed Beclin-1 protein translation in ASM cells, similar to previous finding in another cell type. In vivo, transplantation of miR-384 significantly attenuated Belcin-1 protein levels in ASM cells, resulting in reduced autophagy of ASM cells and attenuation of asthmatic features by OVA. Together, these data suggest that re-expression of miR-384 may reduce augmentation of Beclin-1-dependent autophagy of ASM cells, as a novel promising treatment for asthma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.