Abstract:Objective To investigate the function and mechanism of miR-21/FZD6 axis in extracellular matrix (ECM) remodeling of lung bronchial epithelial cells induced by cigarette smoke extracts (CSE). Methods After 16HBE was treated with CSE, the expression of WNT pathway and ECM remodeling related genes were detected, and miRNA, targeting WNT pathway was screened and verified. After interfering with miR-21 expression, the expression of FZD6 was detected by western blot, and the target relationship between miR-21 and FZD6 was verified by double luciferase assay. The function of the pathway in promoting ECM remodeling by CSE were verified by response experiment.Results CSE treatment could inhibit the activity of WNT pathway and the expression of ECM remodeling-related genes; microRNAs screening and cell validation resulted in the expression of microRNAs-21-5p and FZD6; after CSE treatment, the expression of microRNAs-21-5p was up-regulated, while the expression of FZD6 was down-regulated; interfering with microRNAs-21-5p could enhance the expression of FZD6; double luciferase assay showed that microRNAs-21-5p could target FZD6. The results of response experiments showed that si-FZD6 could promote the expression of genes related to ECM remodeling, and that miR-21 inhibitor could inhibit the expression of genes related to ECM remodeling and partly reverse the effect of si-FZD6 on ECM remodeling.Conclusion CSE can induce the expression of microRNA-21-5p in lung bronchial epithelial cells, weaken the expression of FZD6, inhibit the activity of WNT pathway, and accelerate the process of ECM remodeling in lung bronchial epithelial cells.
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