Functions of Pulmonary Epithelial Integrins: From Development to Disease

Abstract

Signals from integrins are now known to play critical roles in virtually every aspect of the behavior of epithelial cells, including survival, proliferation, maintenance of polarity, secretory differentiation, and malignant transformation. The cells that line the conducting airways and alveoli of the lung, like most surface epithelia, simultaneously express multiple members of the integrin family, including several with broadly overlapping ligand binding specificities. Although multiple integrins on airway epithelial cells may support adhesion to the same ligands, the functional roles of each integrin that has been examined in detail are quite distinct. Findings from mice expressing null mutations of some of these integrins have identified roles for epithelial cells and epithelial integrins in lung development and in the regulation of lung inflammation, macrophage protease expression, pulmonary fibrosis, and the pulmonary edema that follows acute lung injury. Epithelial integrins are thus attractive targets for intervention in a number of common lung disorders.

Morphogenesis in the absence of integrins: mutation of bothDrosophilaβ subunits prevents midgut migration

“…There is a substantial amount of data to suggest that integrins play a role in epithelial architecture and polarity (Sheppard, 2003;Zegers et al, 2003), but the data are conflicting regarding the precise roles. Experiments using 3D epithelial cysts demonstrated a role for integrins in orienting the direction of polarity, but not for establishing distinct apical and lateral membrane domains (Wang et al, 1990;Ojakian and Schwimmer, 1994).…”

αvβ6 Integrin Regulates Renal Fibrosis and Inflammation in Alport Mouse

“…Molecular mechanisms contributing to these events are complex and include misregulation of the transforming growth factor (TGF)-␤ axis, aberrant ECM remodeling, and altered expression and function of cell adhesion receptors of the integrin superfamily. [1][2][3][4][5] Recent studies have revealed important regulatory functions of several integrins and associated molecules in renal epithelial and mesenchymal cells. 3,6 -8 Among the integrins whose expression is strongly increased in renal disease is the TGF-␤-inducible integrin ␣v␤6.…”

INTEGRIN BETA 4 mRNA EXPRESSION LEVELS IN BRONCHIAL ASTHMA PATIENTS

“…Moreover, Sheppard 2003 showed that integrinβ4 expression was clearly elevated after airway epithelialinjuryand could be detected in many cell types, which suggest that integrin β4 might be involved in the repair processes of airway epithelium (Sheppard 2003). Xiang et al, 2014 found thatmutations in 5̄ flanking region of integrin β4 gene result in reduced integrin β4 expression, and that it was related to increased risk of asthma (Xiang et al, 2014).…”