Ya-Ru Yan1, Yang Luo2, Ming Zhong2, Li Shao1. 1. a Department of Allergy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , P.R. China. 2. b Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , P.R. China.
Abstract
Objective: Accumulating evidence suggests that aberrantly expressed microRNAs in airway smooth muscle (ASM) cells could change airway remodeling during the development of asthma. However, the underlying functions of microRNAs in ASM cell proliferation and apoptosis need to be further elucidated. Methods: By using RT-qPCR, miR-216a expression level was examined in the asthmatic patients and non-asthmatic individuals. Cell proliferation assay and flow cytometry analysis were used in ASM cells in which miR-216a was an abnormal expression. MiR-216a predicted to target gene was explored by bioinformatic software, and further analyzed by Western blotting and luciferase reporter assay. Results: Our results demonstrated that miR-216a levels were considerably lower in the ASM cells of asthmatic patients than in those of non-asthmatic individuals. Further study verified that the overexpression of miR-216a markedly suppressed cell proliferation and promoted cell apoptosis, whereas the knockdown of miR-216a had opposite effects in ASM cells. In addition, luciferase reporter assays and Western blotting identified that JAK2 was the direct functional target of miR-216a, and the ectopic expression of JAK2 partially rescued the inhibitory effect of miR-216a in ASM cells. Conclusions: The above data indicate that miR-216a may function as a key regulator of airway remodeling by targeting JAK2, thus suggesting the potential role of miR-216a in the pathogenesis of asthma.
Objective: Accumulating evidence suggests that aberrantly expressed microRNAs in airway smooth muscle (ASM) cells could change airway remodeling during the development of asthma. However, the underlying functions of microRNAs in ASM cell proliferation and apoptosis need to be further elucidated. Methods: By using RT-qPCR, miR-216a expression level was examined in the asthmatic patients and non-asthmatic individuals. Cell proliferation assay and flow cytometry analysis were used in ASM cells in which miR-216a was an abnormal expression. MiR-216a predicted to target gene was explored by bioinformatic software, and further analyzed by Western blotting and luciferase reporter assay. Results: Our results demonstrated that miR-216a levels were considerably lower in the ASM cells of asthmatic patients than in those of non-asthmatic individuals. Further study verified that the overexpression of miR-216a markedly suppressed cell proliferation and promoted cell apoptosis, whereas the knockdown of miR-216a had opposite effects in ASM cells. In addition, luciferase reporter assays and Western blotting identified that JAK2 was the direct functional target of miR-216a, and the ectopic expression of JAK2 partially rescued the inhibitory effect of miR-216a in ASM cells. Conclusions: The above data indicate that miR-216a may function as a key regulator of airway remodeling by targeting JAK2, thus suggesting the potential role of miR-216a in the pathogenesis of asthma.