Skip to main content

Advertisement

Log in

MicroRNA-629-3p Promotes Interleukin-13-Induced Bronchial Epithelial Cell Injury and Inflammation by Targeting FOXA2

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Objective

Asthma is a chronic pulmonary inflammatory disease. MicroRNA (miR)-629-3p expression is reported to be up-regulated in the sputum of asthma patients. Nonetheless, miR-629-3p’s role and mechanism in asthma remain largely unknown. This study is aimed at exploring miR-629-3p’s role in regulating the injury and inflammation of bronchial epithelial cells.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of miR-629-3p and forkhead box a2 (FOXA2) mRNA in 16HBE cells treated with interleukin-13 (IL-13). 16HBE cell viability was evaluated using the cell counting kit-8 (CCK-8) assay, and cell apoptosis was analyzed by a flow cytometer. The levels of C-C motif chemokine ligand 11 (CCL11), C-C motif chemokine ligand 26 (CCL26), C-C motif ligand 2 (CCL-2)/mono-cyte chemotactic protein-1 (MCP-1), interleukin-1 beta (IL-1b), and interleukin 6 (IL-6) in 16HBE cell supernatant were detected through enzyme-linked immunosorbent assay (ELISA). The downstream target genes of miR-629-3p were predicted through bioinformatics. Besides, the targeted relationship between miR-629-3p and FOXA2 mRNA 3′-UTR was verified by dual-luciferase reporter gene assay. Western blot was utilized to determine the regulatory effects of miR-629-3p on the expression of FOXA2 protein in 16HBE cells.

Results

MiR-629-3p expression was significantly enhanced in IL-13-stimulated 16HBE cells while the FOXA2 mRNA and protein levels were significantly down-regulated. The transfection of miR-629-3p mimics inhibited 16HBE cells’ viability, and promoted the apoptosis and the secretion of chemokines CCL11, CCL26, CCL-2/MCP-1, IL-1b, and IL-6 of 16HBE cells, whereas inhibiting miR-629-3p had the opposite effects. Moreover, FOXA2 was identified as a downstream miR-629-3p target, and its overexpression reversed the effects of the miR-629-3p on 16HBE cells.

Conclusion

MiR-629-3p promotes IL-13-induced 16HBE cells’ injury and inflammation by targeting FOXA2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Athari, S. S. (2019). Targeting cell signaling in allergic asthma. Signal Transductuction and Targeted Therapy, 4, 45.

    Article  Google Scholar 

  2. Li, J., Zheng, M., Wang, C., Jiang, J., Xu, C., Li, L., Li, L., Yan, G. & Jin, Y. (2020). Cryptotanshinone attenuates allergic airway inflammation through negative regulation of NF-κB and p38 MAPK. Bioscience, Biotechnology, and Biochemistry, 84(2), 268–278.

    Article  CAS  Google Scholar 

  3. Boulet, L. P.(2018). Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Current Opinion in Pulmonary Medicine, 24(1), 56–62.

    Article  Google Scholar 

  4. Gon, Y., & Hashimoto, S. (2018). Role of airway epithelial barrier dysfunction in pathogenesis of asthma. Allergology International, 67(1), 12–17.

    Article  CAS  Google Scholar 

  5. Bok, S. H., Seo, J. H., Bae, C. S., Kang, B., Cho, S. S., & Park, D. H. (2019). Allium hookeri root extract regulates asthmatic changes through immunological modulation of Th1/Th2‑related factors in an ovalbumin‑induced asthma mouse model. Molecular Medicine Reports, 20(4), 3215–3223.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. McCracken, J. L., Veeranki, S. P., Ameredes, B. T., & Calhoun, W. J. (2017). Diagnosis and management of asthma in adults: a review. JAMA., 318(3), 279–290.

    Article  Google Scholar 

  7. Pan, J., Yang, Q., Zhou, Y., Deng, H., Zhu, Y., Zhao, D. & & Liu, F. (2020). MicroRNA-221 modulates airway remodeling via the PI3K/AKT pathway in OVA-induced chronic murine asthma. Frontiers in Cell and Developmental Biology, 8, 495 Jun 30.

    Article  Google Scholar 

  8. Alharris, E., Alghetaa, H., Seth, R., Chatterjee, S., Singh, N. P., Nagarkatti, M., & Nagarkatti, P. (2018). Resveratrol attenuates allergic asthma and associated inflammation in the lungs through regulation of miRNA-34a that targets FoxP3 in mice. Frontiers in Immunology, 9, 2992.

    Article  CAS  Google Scholar 

  9. Lou, L., Tian, M., Chang, J., Li, F., & Zhang, G. (2020). MiRNA-192-5p attenuates airway remodeling and autophagy in asthma by targeting MMP-16 and ATG7. Biomedicine & Pharmacotherapy, 122, 109692.

    Article  CAS  Google Scholar 

  10. Lou, L., Tian, M., Chang, J., Li, F., & Zhang, G. (2020). MiRNA-192-5p attenuates airway remodeling and autophagy in asthma by targeting MMP-16 and ATG7. Biomedicine & Pharmacotherapy, 122, 109692.

    Article  CAS  Google Scholar 

  11. Li, B. B., Chen, Y. L., & Pang, F. (2020). MicroRNA-30a targets ATG5 and attenuates airway fibrosis in asthma by suppressing autophagy. Inflammation, 43(1), 44–53.

    Article  CAS  Google Scholar 

  12. Maes, T., Cobos, F. A., Schleich, F., Sorbello, V., Henket, M., De Preter, K., Bracke, K. R., Conickx, G., Mesnil, C., Vandesompele, J., Lahousse, L., Bureau, F., Mestdagh, P., Joos, G. F., Ricciardolo, F. L., Brusselle, G. G., & Louis, R. (2016). Asthma inflammatory phenotypes show differential microRNA expression in sputum. Journal of Allergy and Clinical Immunology, 137(5), 1433–1446.

    Article  CAS  Google Scholar 

  13. Aghaei, M., Khodadadian, A., Elham, K. N., Nazari, M., & Babakhanzadeh, E. (2020). Major miRNA involved in insulin secretion and production in beta-cells. International Journal of General Medicine, 13, 89–97.

    Article  CAS  Google Scholar 

  14. Wei, C., Tang, X., Wang, F., Li, Y., Sun, L., & Luo, F. (2019). Molecular characterization of pulmonary defenses against bacterial invasion in allergic asthma: The role of Foxa2 in regulation of β-defensin 1. PLoS One, 14(12), e0226517.

    Article  CAS  Google Scholar 

  15. Zhang, K., Liang, Y., Feng, Y., Wu, W., Zhang, H., He, J., Hu, Q., Zhao, J., Xu, Y., Liu, Z. & & Zhen, G. (2018). Decreased epithelial and sputum miR-221-3p associates with airway eosinophilic inflammation and CXCL17 expression in asthma. American Journal of Physiology-Lung Cellular and Molecular Physiology, 315(2), L253–L264.

    Article  CAS  Google Scholar 

  16. Li, B., Meng, Y. Q., Li, Z., Yin, C., Lin, J. P., Zhu, D. J., & Zhang, S. B. (2019). MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 3286–3296.

    Article  CAS  Google Scholar 

  17. Makita, K., Mikami, Y., Matsuzaki, H., Miyashita, N., Takeshima, H., Noguchi, S., Horie, M., Urushiyama, H., Iikura, M., Hojo, M., Nagase, T. & Yamauchi, Y. (2018). Mechanism of periostin production in human bronchial smooth muscle cells. International Archives of Allergy and Immunology, 175(1-2), 26–35.

    Article  CAS  Google Scholar 

  18. Río-Araiza, V. H. D., Nava-Castro, K. E., Alba-Hurtado, F., Quintanar-Stephano, A., Aguilar-Díaz, H., Muñoz-Guzmán, M. A., Ostoa-Saloma, P., Ponce-Regalado, M. D., & Morales-Montor, J. (2018). Prolactin as immune cell regulator in Toxocara canis somatic larvae chronic infection. Bioscience Reports, 38(4), BSR20180305.

    Article  Google Scholar 

  19. Busse, W. W. (2019). Biological treatments for severe asthma: A major advance in asthma care. Allergology International, 68(2), 158–166.

    Article  CAS  Google Scholar 

  20. Crapster-Pregont, M., Yeo, J., Sanchez, R. L., & Kuperman, D. A. (2012). Dendritic cells and alveolar macrophages mediate IL-13-induced airway inflammation and chemokine production. Journal of Allergy and Clinical Immunology, 129(6), 1621–1627.

    Article  CAS  Google Scholar 

  21. Matsukura, S., Osakabe, Y., Sekiguchi, A., Inoue, D., Kakiuchi, Y., Funaki, T., Yamazaki, Y., Takayasu, H., Tateno, H., Kato, E., Wakabayashi, A., Hayashi, M., Ishii, G., Yamaguchi, F., Tsuchiya, Y., Kasahara, K., Sagara, H., & Kokubu, F. (2016). Overexpression of microRNA-155 suppresses chemokine expression induced by Interleukin-13 in BEAS-2B human bronchial epithelial cells. Allergology International, 65(Suppl), S17–S23.

    Article  Google Scholar 

  22. Ntontsi, P., Papathanassiou, E., Loukides, S., Bakakos, P., & Hillas, G. (2018). Targeted anti-IL-13 therapies in asthma: current data and future perspectives. Expert Opinion on Investigational Drugs, 27(2), 179–186.

    Article  CAS  Google Scholar 

  23. Chen, J., Li, C., Liu, W., Yan, B., Hu, X., & Yang, F. (2019). miRNA-155 silencing reduces sciatic nerve injury in diabetic peripheral neuropathy. Journal of Molecular Endocrinology, 63(3), 227–238.

    Article  CAS  Google Scholar 

  24. Jin, A., Bao, R., Roth, M., Liu, L., Yang, X., Tang, X., Yang, X., Sun, Q., & Lu, S. (2019). microRNA-23a contributes to asthma by targeting BCL2 in airway epithelial cells and CXCL12 in fibroblasts. Journal of Cellular Physiology, 234(11), 21153–21165.

    Article  CAS  Google Scholar 

  25. Bartel, S., La Grutta, S., Cilluffo, G., Perconti, G., Bongiovanni, A., Giallongo, A., Behrends, J., Kruppa, J., Hermann, S., Chiang, D., Pfaffl, M. W., & Krauss-Etschmann, S. (2020). Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development. Allergy., 75(2), 346–356.

    Article  CAS  Google Scholar 

  26. Xiong, T., Du, Y., Fu, Z. & Geng, G. (2019). MicroRNA-145-5p promotes asthma pathogenesis by inhibiting kinesin family member 3A expression in mouse airway epithelial cells. Journal of International Medical Research, 47(7), 3307–3319.

    Article  CAS  Google Scholar 

  27. Zhang, H., Sun, Y., Rong, W., Fan, L., Cai, Y., Qu, Q., Gao, Y. & Zhao, H. (2018). miR-221 participates in the airway epithelial cells injury in asthma via targeting SIRT1. Experimental Lung Research, 44(6), 272–279.

    Article  Google Scholar 

  28. Huo, X., Zhang, K., Yi, L., Mo, Y., Liang, Y., Zhao, J., Zhang, Z., Xu, Y., & Zhen, G. (2016). Decreased epithelial and plasma miR-181b-5p expression associates with airway eosinophilic inflammation in asthma. Clinical & Experimental Allergy, 46(10), 1281–1290.

    Article  CAS  Google Scholar 

  29. Li, B., Meng, Y. Q., Li, Z., Yin, C., Lin, J. P., Zhu, D. J., & Zhang, S. B. (2019). MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 3286–3296.

    Article  CAS  Google Scholar 

  30. Maier, J. A., Lo, Y., & Harfe, B. D. (2013). Foxa1 and Foxa2 are required for formation of the intervertebral discs. PLoS One, 8(1), e55528.

    Article  CAS  Google Scholar 

  31. Li, X., Liu, H., Lv, Y., Yu, W., Liu, X., & Liu, C. (2020). MiR-130a-5p/Foxa2 axis modulates fetal lung development in congenital diaphragmatic hernia by activating the Shh/Gli1 signaling pathway. Life Sciences, 241, 117166.

    Article  CAS  Google Scholar 

  32. Mei, M., Nie, J., Sun, H., Wang, H. & Rong, L. (2020). LncRNA-NEF regulated the hyperoxia-induced injury of lung epithelial cells by FOXA2. American Journal of Translational Research, 12(9), 5563–5574.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Kistemaker, L. E., Hiemstra, P. S., Bos, I. S., Bouwman, S., van den Berge, M., Hylkema, M. N., Meurs, H., Kerstjens, H. A., & Gosens, R. (2015). Tiotropium attenuates IL-13-induced goblet cell metaplasia of human airway epithelial cells. Thorax, 70(7), 668–676.

    Article  Google Scholar 

  34. Choi, W., Choe, S., & Lau, G. W. (2020). Inactivation of FOXA2 by respiratory bacterial pathogens and dysregulation of pulmonary mucus homeostasis. Frontiers in Immunology, 11, 515.

    Article  CAS  Google Scholar 

  35. Salem, M., O’Brien, J. A., Bernaudo, S., Shawer, H., Ye, G., Brkić, J., Amleh, A., Vanderhyden, B. C., Refky, B., Yang, B. B., Krylov, S. N., & Peng, C. (2018). miR-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-versican pathway. Cancer Research, 78(15), 4175–4190.

    Article  CAS  Google Scholar 

  36. Zhang, J., Zhang, Z., Sun, J., Ma, Q., Zhao, W., Chen, X., & Qiao, H. (2019). MiR-942 regulates the function of breast cancer cell by targeting FOXA2. Bioscience Reports, 39(11), BSR20192298.

    Article  CAS  Google Scholar 

  37. Liu, J. H., Li, C., Zhang, C. H., & Zhang, Z. H. (2020). LncRNA-CASC7 enhances corticosteroid sensitivity via inhibiting the PI3K/AKT signaling pathway by targeting miR-21 in severe asthma. Pulmonology, 26(1), 18–26.

    Article  Google Scholar 

  38. Yang, W., Chen, Y., Huang, C., Wang, W., Huang, C., & Li, Y. (2021). MiR-18a inhibits PI3K/AKT signaling pathway to regulate PDGF BB-induced airway smooth muscle cell proliferation and phenotypic transformation. Physiological Research, 70(6), 883.

    Article  Google Scholar 

  39. Cao, J., Wang, X., Wang, D., Ma, R., Li, X., Feng, H., Wang, J., Liu, S., & Wang, L. (2019). PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells. Cancer Cell International, 19, 93.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd (Wuhan, China) for its linguistic assistance during the preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jin Yangli or Zhang Xiaomin.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Ethical Approval

Our study was approved by the Ethics Review Board of YJinxiang People’s Hospital.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jian, G., Yangli, J., Chao, Z. et al. MicroRNA-629-3p Promotes Interleukin-13-Induced Bronchial Epithelial Cell Injury and Inflammation by Targeting FOXA2. Cell Biochem Biophys 80, 457–466 (2022). https://doi.org/10.1007/s12013-022-01072-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-022-01072-6

Keywords

Navigation