The shedding of airway epithelial cells and loss of epithelial functional homeostasis are major pathological characteristics of
asthma; however, the mechanism underlying these pathologies remains obscure. Our previous work showed that there were three variation sites in 5' flanking region of
integrin beta4 in
asthma patients, which was correlated with decreased expression of
integrin beta4 in peripheral leukocytes.
Integrin beta4 is an important structural adhesion molecule on airway epithelia to keep the structural adhesion of epithelial cells. In this work, we further demonstrated that
integrin beta4 expression was downregulated in airway epithelia of
asthma patients. To probe the relationship between imbalanced expression of
integrin beta4 and dysfunction of the airway epithelial cells in
asthma,
integrin beta4 was silenced in human bronchial epithelium cells (16HBE14O) by
integrin beta4 small-interfering RNA lentivirus vector. Upon silencing of
integrin beta4, 16HBE14O cells showed reduced proliferation and
wound repair. Most cells were shown to be arrested in G1 phase after
integrin beta4 silencing, and increased apoptosis was induced in the
integrin beta4-silenced cells. In summary, our results provided compelling evidence that
integrin beta4 was involved in the structural integrity and functional homeostasis of airway epithelial cells. It is likely that downregulation of
integrin beta4 on
asthma airway epithelia contributes to the structural disruption and dysfunction of airway epithelial cells.