AbstractObjective 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.
HU Ting,ZHAO Jun,ZHANG Rong-rong, et al. Effect of miR-21/FZD6 Axis on Extracellular Matrix Remodeling of Lung Bronchial Epithelial Cells Induced[J]. JOURNAL OF CLINICAL RESEARCH, 2019, 36(2): 213-216.
[1] Corlateanu A, Odajiu I, Botnaru V,et al. From smoking to COPD-current approaches[J].Pneumologia,2016, 65(1): 20-23. [2] Sand JM, Knox AJ, Lange P, et al. Accelerated extracellular matrix turnover during exacerbations of COPD[J].Respir Res,2015, 16(1): 69. [3] Kumawat K, Menzen MH, Bos IS, et al. Noncanonical WNT-5A signaling regulates TGF-β-induced extracellular matrix production by airway smooth muscle cells[J].Faseb J,2013, 27(4): 1631-1643.[4] Guo L.WNT/beta-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARdelta/p38 pathway[J].Lab Invest,2016, 96(2): 218-229.[5] Song JL, Nigam P, Tektas SS, et al. microRNA regulation of Wnt signaling pathways in development and disease[J].Cell Signal,2015, 27(7): 1380-1391. [6] Gu W, Yuan Y, Yang H, et al. Role of miR-195 in cigarette smoke-induced chronic obstructive pulmonary disease[J].Int Immunopharmacol,2018, 55: 49-54. [7] 夏为, 董士民. 微小RNA在急性肺损伤中的研究进展[J].医学临床研究, 2015, 32(1):173-176. [8] An CH, Wang XM, Lam HC, et al. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema[J].Am J Physiol Lung Cell Mol Physiol,2012, 303(9): L748-757. [9] 周慧霞, 加尔肯·拉斯拜, 白云峰等. 慢性阻塞性肺疾病长期随访中肺功能的变化及影响因素[J].医学临床研究, 2017, 34(8): 1640-1642. [10] Munoz-Esquerre M, Huertas D, Escobar I, et al. Gene and Protein Expression of Fibronectin and Tenascin-C in Lung Samples from COPD Patients[J].Lung,2015, 193(3): 335-343. [11] Abd El-Fatah MF, Ghazy MA, Mostafa MS, et al. Identification of MMP-9 as a biomarker for detecting progression of chronic obstructive pulmonary disease[J].Biochem Cell Biol,2015, 93(6): 541-547. [12] 柳威, 陈荣昌, 汤彦. COPD患者血清MMP-9、TIMP-1的表达与治疗反应性的相关性研究[J].医学临床研究, 2012, 29(12): 2298-2301. [13] Baarsma HA, K nigshoff M. ‘WNT-er is coming’: WNT signalling in chronic lung diseases[J].Thorax,2017, 72(8): 746-759. [14] Van Pottelberge GR, Mestdagh P, Bracke KR, et al. MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease[J].Am J Respir Crit Care Med,2011, 183(7): 898-906.
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