Silicosis is a very serious occupational disease and it features pathological manifestations of inflammatory infiltration, excessive proliferation of fibroblasts and massive depositions of the extracellular matrix in the lungs. Recent studies described the roles of a variety of microRNAs (miRNAs) in fibrotic diseases. Here, we aimed to explore the potential mechanism of miR-542-5p in the activation of lung fibroblasts. To induce a pulmonary fibrosis mouse model, silica suspension and the miR-542-5p agomir were administered to mice by intratracheal instillation and tail vein injection. We found that miR-542-5p was significantly decreased in mouse fibrotic lung tissues and up-regulation of miR-542-5p visually attenuated a series of fibrotic lesions, including alveolar structural damage, alveolar interstitial thickening and silica-induced nodule formation. The down-regulation of miR-542-5p was also observed in mouse fibroblast (NIH-3T3) treated with transforming growth factor β1 (TGF-β1). The proliferation and migration ability of NIH-3T3 cells were also inhibited by the transfection of miR-542-5p mimic. Integrin α6 (Itga6), reported as a cell surface protein associated with fibroblast proliferation, was confirmed to be a direct target of miR-542-5p. The knockdown of Itga6 significantly inhibited the phosphorylation of FAK/PI3K/AKT. In conclusion, miR-542-5p has a potential function for reducing the proliferation of fibroblasts and inhibiting silica-induced pulmonary fibrosis, which might be partially realized by directly binding to Itga6. Our data suggested that miR-542-5p might be a new therapeutic target for silicosis or other pulmonary fibrosis.

Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play critical roles in some diseases, but how these processes are regulated in silicosis remains limited. Here, we explored the role of miR-1224-5p in a mouse model of silicosis. We showed that the expression of miR-1224-5p is increased both in lung tissues of silica-induced pulmonary fibrosis and fibroblasts exposed to TGF-β1. Repression of miR-1224-5p expression attenuated silica-induced fibrotic progression in vivo and TGF-β1-induced myofibroblast differentiation in vitro. Additionally, we demonstrated that miR-1224-5p facilitated silica-induced pulmonary fibrosis primarily by repressing one of target genes, BECN1, thereby blocking PARK2 translocation to mitochondria and inducing the accumulation of damaged mitochondria. Furthermore, the activation of PDGFR signal mediated by mitochondrial damage and insufficient mitophagy resulted in myofibroblast differentiation. Collectively, these data indicated that miR-1224-5p exerts key functions in silica-induced pulmonary fibrosis and may represent a potential therapeutic target for silicosis.

Background: Under the context that the Chinese government has taken many incentives to promote the development of primary health care (PHC), the extent to which patients choose PHC as their usual source of care (USC) and how patient perceived service quality affects this choice remains unclear. This study aimed to explore potential profiles of patient perceived service quality of PHC, analyse sociodemographic and health-related characteristics among perceived service quality subgroups, and investigate the association between patient perceived service quality and usual source of PHC.Methods: A cross-sectional survey was conducted in Shandong Province, China, from July 2023 to August 2023. 3025 patients were selected using a multistage stratified sampling method. Latent profile analysis was used to explore the profiles of patient perceived service quality of PHC. Multiple logistic regression analysis was adopted to identify the predictors of different profiles, and the binary logistic regression was used to examine the association between perceived service quality profiles and usual source of PHC.Results: The model fitting indices of patient perceived service quality supported three profiles which were as follows: low perceived service quality group at 20.23%, moderate perceived service quality group at 56.50%, and high perceived service quality group at 23.27%. Age, educational level, personal monthly income, and self-rated health were predictors of different profiles. Furthermore, patients reporting high perceived service quality of PHC were more likely to regard PHC as the USC compared with those with low perceived service quality (OR = 2.748, 95% confidence interval = 2.112–3.575).Conclusion: Strengthening patient perceived service quality can encourage them to regard PHC facilities as the USC. PHC facilities should provide customized and tailored health services that focus on individuals’ specific needs and preferences to improve patient perceived service quality.