Liyan Dou1, Wenyu Wang2, Junwei Wang2, Xiaofei Zhang2, Xiaoman Hu2, Weili Zheng2, Kaiyu Han3, Guangyou Wang4. 1. Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Heilongjiang, China. 2. Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China. 3. Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China. hankaiyu2002@163.com. 4. Department of Neurobiology, Harbin Medical University, Heilongjiang, China. wangguangyou@hrbmu.edu.cn.
Abstract
BACKGROUND: Several miRNAs are now known to have clear connections to the pathogenesis of asthma. The present study focused on the potential role of miR-3934 during asthma development. METHODS: miR-3934 was detected as a down-regulated miRNA in basophils by sequencing analysis. Next, the expression levels of miR-3934 in peripheral blood mononuclear cells of 50 asthma patients and 50 healthy volunteers were examined by RT-qPCR methods. The basophils were then treated with AGEs and transfected with miR-3934 mimics. The apoptosis levels were examined by flow cytometry assay; and the expression levels of cytokines were detected using the ELISA kits. Finally, the Western blot was performed to examined the expression of key molecules in the TGF-β/Smad signaling pathway. RESULTS: miR-3934 was down-regulated in the basophils of asthmatic patients. The expression of the pro-inflammatory cytokines IL-6, IL-8 and IL-33 was enhanced in basophils from asthmatic patients, and this effect was partially reversed by transfection of miR-3934 mimics. Furthermore, receiver operating characteristics analysis showed that miR-3934 levels can be used to distinguish asthma patients from healthy individuals. miR-3934 partially inhibited advanced glycation end products-induced increases in basophil apoptosis by suppressing expression of RAGE. CONCLUSION: Our results indicate that miR-3934 acts to mitigate the pathogenesis of asthma by targeting RAGE and suppressing TGF-β/Smad signaling.
BACKGROUND: Several miRNAs are now known to have clear connections to the pathogenesis of asthma. The present study focused on the potential role of miR-3934 during asthma development. METHODS: miR-3934 was detected as a down-regulated miRNA in basophils by sequencing analysis. Next, the expression levels of miR-3934 in peripheral blood mononuclear cells of 50 asthma patients and 50 healthy volunteers were examined by RT-qPCR methods. The basophils were then treated with AGEs and transfected with miR-3934 mimics. The apoptosis levels were examined by flow cytometry assay; and the expression levels of cytokines were detected using the ELISA kits. Finally, the Western blot was performed to examined the expression of key molecules in the TGF-β/Smad signaling pathway. RESULTS: miR-3934 was down-regulated in the basophils of asthmatic patients. The expression of the pro-inflammatory cytokines IL-6, IL-8 and IL-33 was enhanced in basophils from asthmatic patients, and this effect was partially reversed by transfection of miR-3934 mimics. Furthermore, receiver operating characteristics analysis showed that miR-3934 levels can be used to distinguish asthma patients from healthy individuals. miR-3934 partially inhibited advanced glycation end products-induced increases in basophil apoptosis by suppressing expression of RAGE. CONCLUSION: Our results indicate that miR-3934 acts to mitigate the pathogenesis of asthma by targeting RAGE and suppressing TGF-β/Smad signaling.
Authors: Adam Kelvin Alec Wright; Sarah Diver; Jamie McCarthy; Andrew Marvin; Marcia Soares; Tracy Thornton; Michelle Bourne; Michelle Craner; Helen Evans; Sarah Edwards; Sarah Glover; Liesl Carr; Sarah Parker; Salman Siddiqui; David Cousins; Chris Brightling Journal: Allergy Date: 2019-06-28 Impact factor: 13.146
Authors: Terase F Lancefield; Sheila K Patel; Melanie Freeman; Elena Velkoska; Bryan Wai; Piyush M Srivastava; Mark Horrigan; Omar Farouque; Louise M Burrell Journal: PLoS One Date: 2016-09-14 Impact factor: 3.240