Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin

Lung Biology Center, University of California, San Francisco 94143, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 06/1996; 133(4):921-8.
Source: PubMed


The integrin alpha v beta 6 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the beta 6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. Beta 6-/- mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These results suggest that the epithelial integrin alpha v beta 6 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.

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    • "In humans, αv is up-regulated during wound healing (Cavani et al., 1993; Clark et al., 1996). Young β6 -/-mice do not display wound healing defects; however, wound healing is delayed in aged β6 null mice compared to age-matched controls (AlDahlawi et al., 2006; Huang et al., 1996). In contrast, constitutive expression of β6 in the epidermis leads to formation of chronic wounds (Häkkinen et al., 2004). "
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    • "A great number of studies have established that integrin binding is the main prerequisite for latent TGF-β1 activation, in particular in conditions of inflammation and fibrosis [110]. Knocking out integrin subunits that activate TGF-β1, including β6 [113], αv [114], and β8 [115], and mutation of the integrin binding site in LAP [116] all produce defects that are similar to the phenotype of the TGF-β1 knockout mouse [103]. Seminal work of Sheppard and coworkers have shown that β6 integrin was unable to active latent TGF-β1 without a functional cytoplasmic tail that intracellularly links to the actin cytoskeleton [117]. "
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    • "In contrast, the expression of integrin b4 in the epidermis of Col1a2-CTGF transgenic mice was irregularly distributed all around the hyperproliferative epithelial cells (Fig. 1A,B, red). Another epithelial specific integrin, avb6, that is barely detectable in quiescent epithelial cells is rapidly induced upon epithelial injury and imparts increased migratory properties to these cells (Huang et al., 1996). Interestingly, we observed a marked enhancement in the expression of integrin b6 in the epidermis of Col1a2-CTGF transgenic mice compared to littermate controls (Fig. 1C,D) suggesting that these cells might have increased migratory properties. "
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