MICRORNA-221 IS OVEREXPRESSED IN THE EQUINE ASTHMATIC AIRWAY SMOOTH MUSCLE AND MODULATES SMOOTH MUSCLE CELL PROLIFERATION
American Journal of Physiology - Lung cellular and Molecular Physiology
Airway wall remodeling, including hyperplasia and hypertrophy of smooth muscle cells (ASM) leading to increased smooth muscle mass, is considered central to asthma. However, molecular pathways responsible for ASM remodeling remain poorly understood. MicroRNA (miRNA) have emerged as key regulators of inflammatory and repair processes affecting lungs and can down-regulate protein expression by inhibiting target mRNA translation. We therefore hypothesized that miRNAs are involved in ASM remodeling
... d 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. Theirs 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 to asthma remission and controls. MiR-221 induced cell hyper-proliferation 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 ( p53, p21 and p27). In conclusion, we demonstrate 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 novel approach for the treatment of ASM remodeling in asthma.