Expression of integrin cell adhesion receptors during human airway epithelial repair in vivo

Abstract

Airway epithelium is subject to injury during inflammation and exposure to a variety of inhaled and infectious agents. Little is known about the expression of integrins during human airway epithelial regeneration and differentiation after injury. We therefore characterized integrin subunit expression after mechanical injury in an in vivo xenograft model of human bronchial epithelium. On the migrating cells at the edges of surface epithelial wounds, there was increased expression of the alpha v-, beta 5-, beta 6-, and alpha 5-integrin subunits. During the later phase of repair, the increased expression of alpha v-, beta 5-, and beta 6-subunits persisted, but the expression of the beta 8-subunits was restricted to basal cells. In addition, there was a redistribution of the alpha 2- and alpha 6-collagen/laminin-binding integrins to suprabasal epithelial layers. There was no expression of the beta 3- or alpha 4-integrin subunit on reparative epithelium. A similar upregulation of alpha v-, beta 5-, and beta 6-integrin receptor subunits was observed in areas of undifferentiated airway from cystic fibrosis patients. Injured epithelium was found to be significantly more susceptible to gene transfer with a recombinant adenovirus, suggesting that the increased integrin expression has implications for the acquisition of adenovirus infections and for lung-directed gene therapy.

Integrin characterization in pulmonary bronchioles

“…h 3 integrin was found to be absent in mouse Clara cells. h 3 integrins have been previously described to be absent in human bronchiolar epithelium (Damjanovich et al, 1992;Pilewski et al, 1997). During the culture, there seems to be a decrease in a 6 from 24 h to 120 h in culture.…”

“…The absent h 3 integrin in mouse lung and Clara cells could be either due to the non-reactive nature of the antibody or because integrin h 3 was not present. The latter hypothesis is more plausible since h 3 integrin is absent from the human bronchiolar region (Pilewski et al, 1997).…”

Overexpressed proprotein convertase 1/3 induces an epithelial-mesenchymal transition in airway epithelium

“…During the repair process after airway epithelial injury, cells actively synthesise a5-integrin at the leading edge of cells [19,20] and require a functional cooperation of integrins with MMP-14 for cell migration [17]. These proteins are PC substrates and activated MMP-14 can facilitate the maturation of pro-MMP-2 [17].…”

“…Since the upregulation of MMPs, a5-integrin and the ECM proteins collagen and fibronectin are common features of EMT [17][18][19][20], we assessed the expression levels of these genes in mock and PC1/3 cells using realtime PCR. Figure 5a shows that PC1/3 overexpression resulted in markedly enhanced expression of MMP-2, MMP-3, and a5-integrin in NCI-H292 cells, while the expression levels of MMP-1, -7, -9 and -10 were not changed; increased MMP-2 expression was confirmed by Western blotting and zymography ( fig.…”

A multi-domain protein for β1 integrin-targeted DNA delivery

“…Apical expression of ␤ 1 integrins has been observed on epithelial cells during inflammation, wound healing and ischaemia. [15][16][17] Endothelial cells also express apical ␤ 1 integrins, which are involved in interactions with leukocytes when activated during the process of inflammation. 18 In conclusion, ␤ 1 integrins are available to external ligands, especially during clinically relevant conditions.…”