Silencing of ADAM33 restrains proliferation and induces apoptosis of airway smooth muscle cells in ovalbumin-induced asthma model.

A defibrinogen and metalloproteinase 33 (ADAM33) was reported to play an important role in asthma. Furthermore, ADAM33 may play a possible role in airway remodeling due to its high expression in myo-/fibroblasts, epithelium, as well as the airway smooth muscle cells (ASMCs). Thus, the study is supposed to investigate the effect of the downregulation of ADAM33 on the proliferation and apoptosis of ASMCs in allergic asthma. An ovalbumin-induced asthma model in rats was established for investigating the function of the silencing of ADAM33. ASMCs were cultured and divided into four groups after transfection. The messenger RNA and protein expressions of ADAM33 were measured by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Cell proliferation was tested by cell counting kit-8 and cell apoptosis by TdT-mediated dUTP nick-end labeling. The allergic asthma rats showed a large number of inflammatory cell infiltration, airway smooth muscle hypertrophy and hyperplasia, and increased WA t , WA m , and numbers of bronchial smooth muscle nucleus. Additionally, increased numbers of eosinophils and neutrophils, expressions of immunoglobulin E and interleukin-4, content of airway air pressure, and NO, although decreased in expression of interferon-γ, were exhibited in rats with allergic asthma. In our study, upregulated ADAM33 was found, and after the silencing of ADAM33, decreased proliferation and increased apoptosis of ASMCs were observed. The study evidences that silencing of ADAM33 can decrease the proliferation and increase the apoptosis of ASMCs in a rat model of allergic asthma, suggesting ADAM33 represents a potential investigative focus target aiding allergic asthma.