MicroRNA-221 is overexpressed in the equine asthmatic airway smooth muscle and modulates smooth muscle cell proliferation.
Abstract: Airway wall remodeling, including hyperplasia and hypertrophy of smooth muscle (ASM) cells leading to an increased smooth muscle mass, is considered central to asthma. However, molecular pathways responsible for ASM remodeling remain poorly understood. MicroRNAs (miRNAs) have emerged as key regulators of inflammatory and repair processes affecting the lungs and can downregulate protein expression by inhibiting target mRNA translation. We therefore hypothesized that miRNAs are involved in ASM remodeling in asthma by modulating ASM proliferation. We have analyzed the expression of miRNAs in bronchial smooth muscle from asthmatic horses during disease exacerbation and remission and from controls. Their involvement in ASM cell proliferation was then studied. Our results shown that miR-26a, miR-133, and miR-221 were upregulated in ASM from horses with asthma exacerbation compared with asthma remission and controls. MiR-221 induced cell hyperproliferation and reduced the expression of contractile gene markers in ASM cells. These changes were associated with the decreased mRNA expression of cell cycle regulatory genes (, , and ). In conclusion, we demonstrated for the first time an upregulation of miR-221 in asthmatic airway smooth muscle and confirm the involvement of miR-221 in ASM cell proliferation by regulation of the cell cycle arrest genes. Targeting miR-221 network genes may represent a novel approach for the treatment of ASM remodeling in asthma.
Publication Date: 2019-08-07 PubMed ID: 31389734DOI: 10.1152/ajplung.00221.2018Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article investigates the role of microRNA-221 in the airway smooth muscle of asthmatic horses, finding that this particular microRNA becomes overexpressed during asthma flare-ups. The study’s findings suggest that microRNA-221 contributes to cell proliferation in the airway smooth muscle, which could offer up new avenues for treating airway remodeling in asthma.
Background
- Asthma is a chronic inflammatory disease of the airways, leading to airflow obstruction due to swelling and increased mucus production in the airway. One major characteristic of asthma is the thickening of the airways (also known as airway remodeling) caused by proliferation of airway smooth muscle (ASM) cells.
- MicroRNAs (miRNAs) are a type of regulatory RNA molecule that can block the translation of messenger RNAs (mRNAs) into proteins. The researchers suggest that miRNAs could be involved in the remodeling process in asthma by influencing ASM cell proliferation.
Methods
- The researchers collected bronchial smooth muscle samples from both horses with exacerbated asthma and horses in asthma remission. They compared the miRNA expression in these samples with that in healthy controls.
- They then conducted further experiments to study the effect of specific miRNAs on ASM cell proliferation.
Results
- The results showed that miRNAs miR-26a, miR-133, and miR-221 were overexpressed in the ASM cells of horses with exacerbated asthma. In particular, miR-221 induced hyperproliferation of ASM cells and reduced the expression of genes that usually limit cell proliferation.
- The researchers drew attention to miR-221, as their findings indicated that it contributes to the overgrowth of ASM cells during asthma flare-ups by inhibiting the expression of cell cycle regulatory genes.
Conclusion
- This study suggests that miR-221 could be a key player in the airway remodeling observed in asthma. It offers preliminary evidence that targeting the network of genes regulated by miR-221 could be a novel approach for treating ASM remodeling in asthma.
Cite This Article
APA
Issouf M, Vargas A, Boivin R, Lavoie JP.
(2019).
MicroRNA-221 is overexpressed in the equine asthmatic airway smooth muscle and modulates smooth muscle cell proliferation.
Am J Physiol Lung Cell Mol Physiol, 317(6), L748-L757.
https://doi.org/10.1152/ajplung.00221.2018 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada.
MeSH Terms
- Airway Remodeling / physiology
- Animals
- Asthma / genetics
- Asthma / metabolism
- Asthma / pathology
- Cell Proliferation
- Cells, Cultured
- Female
- Horses
- Male
- MicroRNAs / genetics
- Muscle, Smooth, Vascular / cytology
- Signal Transduction
Grant Funding
- MOP-102751 / CIHR
Citations
This article has been cited 5 times.- Xiao B, Li L, Yao D, Mo B. Noncoding RNAs in asthmatic airway smooth muscle cells. Eur Respir Rev 2023 Jun 30;32(168).
- Zhou J, Zhang N, Zhang W, Lu C, Xu F. The YAP/HIF-1α/miR-182/EGR2 axis is implicated in asthma severity through the control of Th17 cell differentiation. Cell Biosci 2021 May 12;11(1):84.
- Sisia G, Giudice E, Attanzio A, Briglia M, Piccione G, Trunfio C, Arfuso F. Exosome and miRNA Content Engagement in the Physical Exercise Response: What Is Known to Date in Atheltic Horses?. Int J Mol Sci 2026 Jan 4;27(1).
- Zimbru RI, Zimbru EL, Bojin FM, Haidar L, Andor M, Harich OO, Tănasie G, Tatu C, Mailat DE, Zbîrcea IM, Hirtie B, Uța C, Bănărescu CF, Panaitescu C. Connecting the Dots: How MicroRNAs Link Asthma and Atherosclerosis. Int J Mol Sci 2025 Apr 10;26(8).
- Zhang H, Yan HL, Li XY, Guo YN. TNFSF14, a novel target of miR-326, facilitates airway remodeling in airway smooth muscle cells via inducing extracellular matrix protein deposition and proliferation. Kaohsiung J Med Sci 2020 Jul;36(7):508-514.
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