Wound repair and anti-oxidative capacity is regulated by ITGB4 in airway epithelial cells

Abstract

Integrin beta 4 (ITGB4) is a structural adhesion molecule which engages in maintaining the integrity of airway epithelial cells. Its specific cytomembrane structural feature strongly indicates that ITGB4 may engage in many signaling pathways and physiologic processes. However, in addition to adhesion, the specific biologic significance of ITGB4 in airway epithelial cells is almost unknown. In this article, we investigated the expression and functional properties of ITGB4 in airway epithelial cells in vivo and in vitro. Human bronchial epithelial cell line (16HBE14O-cells) and primary rat tracheal epithelial cells (RTE cells) were used to determine ITGB4 expression under ozone tress or mechanical damage, respectively. An ovalbumin (OVA)-challenged asthma model was used to investigate ITGB4 expression after antigen exposure in vivo. In addition, an ITGB4 overexpression vector and ITGB4 silence virus vector were constructed and transfected into RTE cells. Then, wound repair ability and anti-oxidation capacity was evaluated. Our results demonstrated that, on the edge of mechanically wounded cell areas, ITGB4 expression was increased after mechanical injury. After ozone stress, upregulation expression of ITGB4 was also detected. In the OVA-challenged asthma model, ITGB4 expression was decreased on airway epithelial cells accompanying with structural disruption and damage of anti-oxidation capacity. Besides, our study revealed that upregulation of ITGB4 promotes wound repair ability and anti-oxidative ability, while such abilities were blocked when ITGB4 was silenced. Taken together, these results showed that ITGB4 was a new interesting molecule involved in the regulation of wound repair and anti-oxidation processes for airway epithelial cells.

Analysis on the Relevance of Asthma Susceptibility with the Alteration of Integrin β 4 Expression

“…The integrin β4 gene knock-out mice were shown to have cell cycle and adhesion defect[29]. As the first cell barrier to outer allergens, the airway epithelial cells showed a decreased wound repair and anti-oxidation ability after integrin β4 was downregulated[26], [30], [31]. Furthermore, downregulation of integrin β4 expression in airway epithelial cells could impair the antigen presentation ability of these cells, which further regulates airway inflammation reaction in allergic asthma[32].…”

Downregulation of Integrin β4 Decreases the Ability of Airway Epithelial Cells to Present Antigens

“…Our previous work demonstrated that structural adhesion molecule integrin β4 (ITGB4) is downregulated in asthma airway epithelial cells. As the first cell barrier to outer allergens, the airway epithelial cells showed a decreased wound repair and anti-oxidation ability after ITGB4 was downregulated [14], [15]. ITGB4 is an important adhesion molecule that mediates the anchoring of airway epithelial cells to the basal membrane.…”

ITGB4 deficiency induces senescence of airway epithelial cells through p53 activation

“…The long cytoplasmic domain of an ITGB4 subunit can recruit a series of signaling molecules that influence the functional conditions of airway epithelial cells . By RNA interference, ITGB4 deficiency inhibits the cell division cycle and proliferation in vitro . ITGB4 has also been shown to be associated with aging in many different cells .…”

“…ITGB4 is located at the basal surface of airway epithelial cells in hemi‐desmosome structures which mediate the stable adhesion of airway epithelial cells to the underlying basement membrane component laminin‐5 . The long cytoplasmic domain of an ITGB4 subunit could recruit a series of signaling molecules and thereby influences the proliferation, damage repair and oxidative stress of epithelial cells . Besides, it has also been demonstrated that after house dust mite stress, ITGB4 defects in airway epithelial cells conferred increased airway hyper‐responsiveness and aggravated airway inflammation compared with wild‐type mice .…”