Background. Overexpression of the MUC5B protein is associated with idiopathic pulmonary fibrosis (IPF), but little information is available regarding the pathogenic effects and regulatory mechanisms of overexpressed MUC5B in IPF. Main Body. The overexpression of MUC5B in terminal bronchi and honeycomb cysts produces mucosal host defensive dysfunction in the distal airway which may play an important role in the development of IPF. This review addresses the possible association of overexpression of MUC5B, with MUC5B promoter polymorphism, MUC5B gene epigenetic changes, effects of some transcriptional factors, and inflammatory mediators in IPF. In addition, the associated signaling pathways which may influence the expression of MUC5B are also discussed. Conclusion. This work has important implications for further exploration of the mechanisms of overexpression of MUC5B in IPF, and future personalized treatment.

Background Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity and contribute to immunosuppressive microenvironment during tumor development including lung cancer. Accumulating evidence shows microRNAs (miRNAs) affect tumor-expanded MDSC accumulation and function in tumor microenvironment and favor solid tumor growth. Herein, we aim to characterize the role of miR-21 in regulating the accumulation and activity of MDSCs in lung cancer. Methods The proportions of MDSCs, T helper cells (Th), and cytotoxic T lymphocytes (CTL) were evaluated by flow cytometric analyses of peripheral blood and tumor tissues collected from Lewis lung-cancer-bearing mice. T cell proliferation assay was performed in CD4+ or CD8+ T cells cocultured with MDSCs. MDSC apoptosis was examined by flow cytometric analysis. The levels of IL-10, TGF-β, and GM-CSF in mouse serum were determined by ELISA. miR-21 targeting RUNX1 and RUNX1 interaction with YAP were evaluated by RIP, dual-luciferase reporter gene, and ChIP assays. Results MiR-21 inhibition by its antagomir reduced the proportion of MDSCs, increased the proportion of Th and CTL in peripheral blood and tumor tissues of Lewis lung-cancer-bearing mice, protected Th and CTL from the suppression of MDSCs, increased apoptosis of MDSCs, but reduced IL-10, TGF-β and GM-CSF levels in mouse serum. RUNX1 could transcriptionally inhibit the YAP expression, whereas miR-21 targeting RUNX1 led to elevated YAP expression levels. Mechanistic investigation showed that miR-21 maintained MDSC accumulation in tumor microenvironment and promoted immunosuppressive ability of MDSCs in Lewis lung-cancer-bearing mice by down-regulating RUNX1and up-regulating YAP. Conclusions Taken together, the study provides evidence that targeting miR-21 in MDSCs may be developed as an immunotherapeutic approach to combat lung cancer development.

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A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (P<0.01), and the concentration in the PAM group was significantly lower than that in the plasmid control group (P<0.01). Based on our findings it is possible that the SLC34A2 gene mutation is the cause of the pathogenic changes observed in PAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo.

Acute respiratory distress syndrome (ARDS) induced by sepsis contributes remarkably to the high mortality rate observed in intensive care units, largely due to a lack of effective drug therapies. Histone deacetylase 6 (HDAC6) is a class-IIb deacetylase that modulates non-nuclear protein functions via deacetylation and ubiquitination. Importantly, HDAC6 has been shown to exert anti-cancer, anti-neurodegeneration, and immunological effects, and several HDAC6 inhibitors have now entered clinical trials. It has also been recently shown to modulate inflammation, and HDAC6 inhibition has been demonstrated to markedly suppress experimental sepsis. The present review summarizes the role of HDAC6 in sepsis-induced inflammation and endothelial barrier dysfunction in recent years. It is proposed that HDAC6 inhibition predominantly ameliorates sepsis-induced ARDS by directly attenuating inflammation, which modulates the innate and adaptive immunity, transcription of pro-inflammatory genes, and protects endothelial barrier function. HDAC6 inhibition protects against sepsis-induced ARDS, thereby making HDAC6 a promising therapeutic target. However, HDAC inhibition may be associated with adverse effects on the embryo sac and oocyte, necessitating further studies.