MiR-34c-5p plays a protective role in chronic obstructive pulmonary disease via targeting CCL22

Abstract

Objective: To study the role of miR-34c-5p targeting CCL22 in affecting the progression of chronic obstructive pulmonary disease (COPD). Methods: The dual-luciferase reporter gene assay was applied to verify the targeting relationship of miR-34c-5p and CCL22. The rats were randomly assigned into Control, COPD, COPD + empty plasmids, COPD + agomir, COPD + CCL22 shRNA and COPD + agomir + CCL22 groups. COPD model was built by using cigarette smoke exposure and LPS instillation. After 28 days, the pulmonary function was examined. ELISA method was used to detect TNF-α and IL-8 levels in bronchoalveolar lavage fluid (BALF), HE staining and Masson staining to observe the pathomorphological changes of lung tissues, qRT-PCR and/or Western blot to determine miR-34c-5p and CCL22 levels, and immunohistochemical staining to measure the expression of MMP-9 and TIMP-1. Results: MiR-34c-5p could target CCL22 to down-regulate its expression. Both miR-34c-5p agomir and CCL22 shRNA could reduce breathing frequency (f), airway resistance (RI), and the levels of IL-8 and TNF-α in BALF of COPD rats with increased Cydn (dynamic lung compliance) and PIF (peak inspiratory flow). Besides, the inflammatory cell infiltration, rupture of partial alveolus, enlarged alveolar cavity, and increased deposition of collagen fibers were observed in COPD rat tissues, with rise in mean linear intercept (MLI) and reduction in mean alveolar number (MAN), which could be reversed by miR-34c-5p agomir or CCL22 shRNA. Conclusion: MiR-34c-5p may promote inflammation response and maintain the protease-antiprotease balance via targeting CCL22, which provides scientific basis for the clinical treatment of COPD.

Keywords:

• miR-34c-5p
• CCL22
• chronic obstructive pulmonary disease