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• W2971317864 abstract "The only effective clinical treatment for many end-stage lung diseases is lung transplantation. However, chronic rejection of transplanted lung affects the long-term efficacy of lung transplantation to a large extent, thereby limiting the clinical application of lung transplantation. Occlusive bronchiolitis (OB) is a major cause of chronic functional loss of the transplanted lung. However, the OB pathogenesis remains unclear. Therefore, studying the OB pathogenesis and finding effective intervention methods are highly important. This study analyzed changes in the expression profile of microRNAs and transcription factors in mice with OB after orthotopic tracheal transplantation. miR-27a-3p was upregulated in lung tissue 20 days after transplantation. Transcription factor microarray analysis revealed that Smad3 was significantly downregulated. A miRNA–mRNA interaction network was constructed, and specific regulatory effects of miR-27a-3p on Smad3 were found. Smad3 was strongly associated with tumorigenesis and organ fibrosis. Compared with the control group, miR-27a-3p inhibited the epithelial–mesenchymal transformation (EMT) of lung epithelial cells. In addition, miR-27a-3p inhibition promoted the invasion and migration of lung epithelial cells. Dual luciferase reporter gene assay showed that miR-27a-3p can regulate the promoter activity of Smad3. MiR-27a-3p also inhibited the expression of inflammatory cytokines. Western blot results showed that miR-27a-3p can upregulate the E-cadherin expression and downregulate the expression of vimentin, fibronectin, and α-SMA. By studying the OB pathogenesis, we found that inhibition or alteration of the occurrence of EMT may reduce the proportion of chronic rejection of lung transplantation. MiR-27a-3p may also be developed as a new drug for the OB therapy. This finding will provide many possibilities for OB treatment and improve the prognosis of patients with OB." @default.
• W2971317864 created "2019-09-05" @default.
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• W2971317864 date "2019-08-27" @default.
• W2971317864 modified "2023-10-18" @default.
• W2971317864 title "MiR-27a-3p downregulation contributes to the development of occlusive bronchiolitis" @default.
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• W2971317864 doi "https://doi.org/10.1007/s12192-019-01026-7" @default.
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