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The present study aimed to investigate the effects of PCI-34051-induced human bronchial epithelial cells (HBECs)-derived exosomes (PCI-Exo) on human bronchial smooth muscle cells (HBSMCs) and the key exosomal miRNAs involved in this process. Blank exosomes (Exo) and PCI-Exo were extracted from HBECs treated with PBS and PCI-34051, respectively. RNA-sequencing was performed to uncover the miRNA expression profile affected by PCI-Exo. The MTT, flow cytometry and TUNEL assays were performed to reveal the effect of PCI-34051 and PCI-Exo on the proliferation and apoptosis of HBSMCs. Western blotting and qRT-PCR were used for detecting protein and mRNA expression. A total of 25 exosomal miRNAs consisted of 17 down-regulated and eight up-regulated miRNAs were differentially expressed among PCI-Exo and Exo. Target genes of the exosomal miRNAs were mainly associated with signal transduction, cell adhesion, microRNAs in cancer, and ECM receptor interaction. miR-381-3p was identified as the most significant upregulated differential miRNA in PCI-Exo after qRT-PCR validation and could be transferred to HBSMCs by PCI-Exo. PCI-Exo treatment inhibited the proliferation but induced the apoptosis of HBSMCs. TGFβ3 was identified as a target gene of miR-381-3p which could directly bind to the 3′UTR of TGFβ3 mRNA. After transfecting the miR-381-3p mimic into HBSMCs, the proliferation inhibition and apoptosis rate of HBSMCs was significantly increased, and siTGFβ3 transfection showed similar effects. Moreover, miR-381-3p overexpression could not only decrease the expression of α-SMA, FN1 and collagen I but also increase that of E-cadherin in HBSMCs. Our findings suggested that PCI-Exo could hinder the proliferation and obviously induce the apoptosis of HBSMCs, and its mechanisms might partly be attributable to the reduction of TGFβ3 level by up-regulating exosomal miR-381-3p expression. These results may be vital for the treatment of lung related-diseases, especially asthma. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease that has been extensively studied for many years. However, finding a complete cure remains a significant challenge. Protein acetylation, especially histone acetylation, plays a significant role in the anti-asthma process. Histone deacetylation inhibitors (HDACi) have been shown to have a curative effect on asthma in clinical practice. An asthmatic mouse model was created by ovalbumin induction. Proteome and acetylproteome analysis were performed on lung tissues. HDACi were tested in the asthmatic mice. A total of 5346 proteins and 581 acetylation sites were identified, among which 154 proteins and 68 acetylation peptides were significantly altered by asthma. Many activated and deactivated processes, pathways, and protein groups were identified through bioinformatics analysis. Sequence motif preference analysis gave rise to a novel Kacrelated core histone region, -KAXXK-, which was postulated as a key regulatory unit of histone acetylation. Asthma involves a variety of proteome dynamics and is controlled by protein lysine acetylation through the core motif -KAXXK-. These findings provide novel avenues to target and treat asthma. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common chronic health conditions in children, and social determinants are thought to be important risk factors. We used Georgia data from the Behavioral Risk Factors Surveillance Survey (BRFSS), and data from the Georgia hospital and emergency department survey for children with a diagnosis of asthma. All data were from the years 2011 to 2016. SAS and SUDAAN were used to calculate weighted prevalence estimates and to perform univariate and multivariate analysis of the association between social determinants, demographic characteristics, other potential risk factors, and asthma-related outcomes. The prevalence of asthma is higher in African-American children and when the parental income is less than $75,000 per year. A multivariate analysis adjusting for ethnicity, parental income, and sex found that the strongest independent predictor of asthma was African-American race (aOR 2.9, 95% CI 1.5–5.8). African-American and multiracial children also experienced extremely high burdens due to asthma related hospitalizations and emergency department visits, with rates two to five times higher than children in other groups. The secular trend for ED visits and hospitalizations is declining. African-American race is an independent predictor of asthma in children in Georgia, and African-American and multiracial children experience a greater burden of asthma than children of other races. Programmatic efforts at the state and national level to improve access, adherence, and knowledge about asthma are important if we are to continue to improve outcomes for these children. [ABSTRACT FROM AUTHOR]