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Conditional ablation of integrin alpha-6 in mouse epidermis leads to skin fragility and inflammation.

Abstract : Hemidesmosomes (HDs) are essential anchorage junctions which mediate the firm attachment of epithelia to the underlying basement membranes, of which one main component is the integrin α6β4. These specific junctions are also able to trigger signalling pathways, via the recruitment and interactions of signalling molecules with HD components such as the cytoplasmic tail of the β4 integrin or the plakin plectin. HDs must also assemble and disassemble depending on the tissue context for example during tissue remodelling. Alterations of HD components or their loss result in skin blistering disorders known as epidermolysis bullosa. Since mice lacking integrin α6 die at birth with severe skin blistering, we have produced a mouse line in which epidermal deletion of integrin α6 can be controlled by tamoxifen injection. We observed that the deletion was mosaic, but that hairless skin such as ears, tails and paws were affected and showed chronic inflammation associated with hyperproliferation, and expression of laminin-111. Interestingly, two cytokines, amphiregulin and epiregulin, previously found increased in integrin α6 deficient cultured keratinocytes, were also increased here in the affected skin. In detached areas, we validate clearly that the absence of integrin α6 leads to a delocalisation of plectin, and the complete disappearance of HD structures.
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Contributor : Hervé De Villemeur Connect in order to contact the contributor
Submitted on : Thursday, November 4, 2010 - 5:02:40 PM
Last modification on : Tuesday, March 29, 2022 - 10:32:59 AM



Cristina Niculescu, Gitali Ganguli-Indra, Véronique Pfister, Valérie Dupé, Nadia Messaddeq, et al.. Conditional ablation of integrin alpha-6 in mouse epidermis leads to skin fragility and inflammation.. Eur J Cell Biol, 2011, 90 (2-3), pp.270-7. ⟨10.1016/j.ejcb.2010.09.003⟩. ⟨inserm-00532916⟩



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