miR-142-5p and miR-130a-3p regulate pulmonary macrophage polarization and asthma airway remodeling
Jianting Shi
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Equal contributors.
Contribution: Methodology, Project administration, Writing - original draft, Writing - review & editing
Search for more papers by this authorMing Chen
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Equal contributors.
Contribution: Formal analysis, Funding acquisition, Writing - original draft
Search for more papers by this authorLihua Ouyang
Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Data curation, Formal analysis, Visualization
Search for more papers by this authorQiujie Wang
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Investigation, Software
Search for more papers by this authorYimin Guo
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Data curation, Investigation
Search for more papers by this authorLinjie Huang
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Investigation, Software
Search for more papers by this authorCorresponding Author
Shanping Jiang
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Correspondence
Shanping Jiang, Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
E-mail: [email protected]
Contribution: Conceptualization, Funding acquisition, Supervision
Search for more papers by this authorJianting Shi
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Equal contributors.
Contribution: Methodology, Project administration, Writing - original draft, Writing - review & editing
Search for more papers by this authorMing Chen
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Equal contributors.
Contribution: Formal analysis, Funding acquisition, Writing - original draft
Search for more papers by this authorLihua Ouyang
Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Data curation, Formal analysis, Visualization
Search for more papers by this authorQiujie Wang
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Investigation, Software
Search for more papers by this authorYimin Guo
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Data curation, Investigation
Search for more papers by this authorLinjie Huang
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Contribution: Investigation, Software
Search for more papers by this authorCorresponding Author
Shanping Jiang
Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Correspondence
Shanping Jiang, Department of Respiratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
E-mail: [email protected]
Contribution: Conceptualization, Funding acquisition, Supervision
Search for more papers by this authorAbstract
Macrophages are key regulators of the development and progression of asthma, facilitating deleterious airway remodeling in affected patients. Immune cell function is tightly regulated by microRNAs (miRNAs), but how these miRNAs impact macrophage-mediated airway remodeling in the context of asthma remains to be determined. In this study, we utilized an ovalbumin (OVA)-based murine model of asthma to evaluate the importance of miRNAs within these macrophages. We found that macrophages from mice that had been sensitized with and exposed to OVA expressed higher levels of M2-like phenotypic markers and exhibited significantly altered expression of both miR-142-5p and miR-130a-3p. When these isolated pulmonary macrophages were cultured in vitro, we determined that transfecting them with miR-142-5p antisense oligonucleotide (ASO) or miR-130a-3p mimics was sufficient to inhibit the ability of interleukin-4 to induce M2 cytokine production. We additionally confirmed the in vivo relevance of these miRNAs in a Ccr2−/− murine model system mimicking asthma. Specifically, we determined that transfecting monocytes with miR-142-5p ASO and/or miR-130a-3p mimics was sufficient to disrupt the ability of these cells to promote airway remodeling. As such, these findings reveal that miR-142-5p and miR-130a-3p dysregulation are important factors governing the polarization of macrophages and associated airway remodeling in OVA-sensitized mice.
CONFLICT OF INTEREST
The authors declare no competing financial interests.
Supporting Information
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