Original Article

MiRNA-21 Regulates Bronchial Epithelial Cell Proliferation by Activating Tgfβ1/Smad Signaling Pathway and Its Correlation with Asthma Severity in Children

Abstract

Background: This research was designed to probe into the role of miRNA-21 in the pathogenesis of childhood asthma and its correlation with the severity.

Methods: Fifty-four children with bronchial asthma admitted to the Third Affiliated Hospital of Qiqihar Medical University from Jun 2018 to Dec 2019 were included. Forty nine healthy children underwent physical examination at this time period were also enrolled. The miR-21 expression in peripheral blood serum was analyzed by qRT-PCR. The relationship between the expression and severity of asthma in children was explored by Spearman correlation analysis and ROC curve. Bronchial epithelial cell lines were cultured in vitro and divided into blank control group, negative control group and miR-21 inhibition and activation group. The changes of cell proliferation after treatment were detected by CCK-8 test in different groups. The expression of TGF-β1/Smad signaling pathway protein in cells was assessed by Western blot (WB).

Results: Compared with that of healthy children, the miR-21 expression in peripheral blood serum of asthmatic children was higher (P<0.001). MiR-21 expression was positively correlated with the severity of illness (r=0.853, P<0.001). The results of cell experiments in vitro signified that miR-21 can promote the proliferation of bronchial epithelial cells, and may be involved in regulating the expression of TGF-β1/ Smad3 signaling pathway, thus affecting cell proliferation.

Conclusion: miRNA-21 regulates the proliferation of bronchial epithelial cells by activating TGFβ1/Smad signaling pathway. And it is positively correlated with the severity of asthma in children.

1. Barnes PJ (2018). Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol, 18(7): 454-466.
2. Tarlo SM, Malo JL (2006). An ATS/ERS report: 100 key questions and needs in occupational asthma. Eur Respir J, 27(3): 607-614.
3. National Cooperative Group on Childhood Asthma; Institute of Environmental Health and Related Product Safety, Chi-nese Center for Disease Control and Prevention; Chinese Center for Disease Control and Prevention (2013). Third na-tionwide survey of childhood asthma in urban areas of China. Zhonghua Er Ke Za Zhi, 51(10): 729-735.
4. GBD 2015 Chronic Respiratory Disease Collaborators (2017). Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmo-nary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med, 5(9): 691-706.
5. Tai A, Tran H, Roberts M, et al (2014). Out-comes of childhood asthma to the age of 50 years. J Allergy Clin Immunol, 133(6): 1572-8.e3.
6. Tai A (2015). Childhood asthma and chron-ic obstructive pulmonary disease: out-comes until the age of 50. Curr Opin Aller-gy Clin Immunol, 15(2): 169-174.
7. Iosifidis T, Sutanto EN, Buckley AG, et al (2020). Aberrant cell migration contrib-utes to defective airway epithelial repair in childhood wheeze. JCI Insight, 5(7): e133125.
8. Perry MM, Adcock IM, Chung KF (2015). Role of microRNAs in allergic asthma: present and future. Curr Opin Allergy Clin Immunol, 15(2): 156–162.
9. LuLF, ListonA (2009). MicroRNA in the immune system, microRNA as an im-mune system. Immunology, 127(3): 291–298.
10. Lee HY, Lee HY, Choi JY, et al (2017). In-hibition of MicroRNA-21 by an antago-mir ameliorates allergic inflammation in a mouse model of asthma. Exp Lung Res, 43(3): 109-119.
11. Sawant DV, Yao W, Wright Z, et al (2015). Serum MicroRNA-21 as a Biomarker for Allergic Inflammatory Disease in Chil-dren. Microrna, 4(1): 36-40.
12. Hammad Mahmoud Hammad R, Hamed DHED, Eldosoky MAER, et al (2018). Plasma microRNA-21, microRNA-146a and IL-13 expression in asthmatic chil-dren. Innate Immun, 24(3): 171-179.
13. Zhang X, Liu C, Li H, et al (2020). Effects of miR-21 on proliferation and apoptosis of WT cells via PTEN/Akt pathway. Exp Ther Med, 19(3): 2155-2160.
14. Zhou X, Xiong J, Lu S, et al (2019). Inhibi-tory Effect of Corilagin on miR-21-Regulated Hepatic Fibrosis Signaling Pathway. Am J Chin Med, 47(7): 1541-1569.
15. Yang K, Hu X (2019). Research progress on miR-21 in heart diseases. Zhejiang Da Xue Xue Bao Yi Xue Ban, 48(2): 214-218.
16. Lewis CC, Yang JY, Huang X, et al (2008). Disease-specifific gene expression profi-filing in multiple models of lung disease. Am J Respir Crit Care Med, 177(4): 376–387.
17. Jiang C, Yu H, Sun Q, et al (2016). Extracel-lular microRNA-21 and microRNA-26a increase in body fluids from rats with an-tigen induced pulmonary inflammation and children with recurrent wheezing. BMC Pulm Med, 16: 50.
18. Elbehidy RM, Youssef DM, El-Shal AS, et al (2016). MicroRNA-21 as a novel bi-omarker in diagnosis and response to therapy in asthmatic children. Mol Immu-nol, 71: 107-114.
19. Wang H, Tan Z, Hu H, et al (2019). Mi-croRNA-21 promotes breast cancer pro-liferation and metastasis by targeting LZTFL1. BMC Cancer, 19(1): 738.
20. Kang HY (2013). MicroRNA-21 regulates stemness in cancer cells. Stem Cell Res Ther, 4(5): 110.
21. Zheng W, Zhao J, Tao Y, et al (2018). Mi-croRNA-21: A promising biomarker for the prognosis and diagnosis of non-small cell lung cancer. Oncol Lett, 16(3): 2777-2782.
22. Wang S, Wan X, Ruan Q (2016). The Mi-croRNA-21 in Autoimmune Diseases. Int J Mol Sci, 17(6): 864.
23. Sims EK, Lakhter AJ, Anderson-Baucum E, et al (2017). MicroRNA 21 targets BCL2 mRNA to increase apoptosis in rat and human beta cells. Diabetologia, 60(6): 1057-1065.
24. Jiang LB, Tian L, Zhang CG (2018). Bone marrow stem cells-derived exosomes ex-tracted from osteoporosis patients inhibit osteogenesis via microRNA-21/SMAD7. Eur Rev Med Pharmacol Sci, 22(19): 6221-6229.
25. Liu RH, Ning B, Ma XE, et al (2016). Regu-latory roles of microRNA-21 in fibrosis through interaction with diverse path-ways. Mol Med Rep, 13(3): 2359–2366.
26. Watanabe K, Narumi T, Watanabe T, et al (2020). The association between mi-croRNA-21 and hypertension-induced cardiac remodeling. PLoS One, 15(2): e0226053.
27. Grainger DJ, Mosedale DE, Metcalfe JC (2000). TGF-beta in blood: a complex problem. Cytokine Growth Factor Rev, 11(1-2): 133-145.
28. Ojiaku CA, Yoo EJ, Panettieri RA Jr (2017). Transforming Growth Factor β1 Func-tion in Airway Remodeling and Hyperre-sponsiveness. The Missing Link? Am J Respir Cell Mol Biol, 56(4): 432-442.
29. Yang YC, Zhang N, Van Crombruggen K, et al (2012). Transforming growth factor-beta1 in inflammatory airway disease: a key for understanding inflammation and remodeling. Allergy, 67(10): 1193-1202.
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IssueVol 50 No 10 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v50i10.7497
Keywords
Childhood asthma MicroRNA Proliferation Transforming growth factor β1
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How to Cite
1.
Kang Y, Bai M, Deng L, Fan L, Wang X. MiRNA-21 Regulates Bronchial Epithelial Cell Proliferation by Activating Tgfβ1/Smad Signaling Pathway and Its Correlation with Asthma Severity in Children. Iran J Public Health. 2021;50(10):1973-1982.