miR-25 expression inhibits proliferation and supports a healthy contractile phenotype in a mouse model of allergic inflammation
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Authors
Hall, Jennifer
Issue Date
2016
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Asthma is a respiratory illness that can be primarily characterized by airway remodeling, airway hyperresponsiveness, and inflammation. While current treatments help to ease symptoms, they do little to treat these underlying causes of asthma. This results in poorly controlled symptoms and raises the need for novel therapeutic targets. One such potential target is miR-25, a microRNA demonstrated in human airway smooth muscle cells to inhibit key cell division pathways. This study aims to test the hypothesis that miR-25 regulates airway smooth muscle phenotypes in a mouse model of allergic inflammation. To investigate the role of miR-25 in proliferation, tissue samples were obtained from second and third generation of transgenic mice in which miR-25 overexpression was targeted to smooth muscle cells (TgSM-miR-25) and wild-type (WT) mice treated with ovalbumin or an adjuvant control. Protein samples from tissues were subjected to Western blot analysis using proliferating cell nuclear antigen or cyclin D1 antibodies. To determine the effects of miR-25 on contractile protein expression, blots from the above experiment were re-probed with smooth muscle myosin heavy chain and smooth muscle myosin heavy chain. In lung tissue from ovalbumin-treated TgSM-miR-25 mice, proliferating cell nuclear antigen expression was significantly decreased compared to the wild-type group. Additionally, smooth muscle myosin heavy chain and smooth muscle-?-actin protein levels were significantly increased in the same tissues. Together these data provide evidence that miR-25 mediates airway smooth muscle phenotype in mice by inhibiting airway smooth muscle cell division and contributed to the development of
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a contractile phenotype. Thus, miR-25 may be a novel therapeutic target for the development of new asthma therapies.
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In Copyright