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The integrin αv-TGFβ signaling axis is necessary for epidermal proliferation during cutaneous wound healing.

ABSTRACT: Proliferation and migration of epidermal keratinocytes are essential for proper cutaneous wound closure after injury. αv integrins and several of their ligands-vitronectin, TGFβ and thrombospondin-are up-regulated in healing wounds. However, the role of αv integrins in wound re-epithelialization is unknown. Here, we show that genetic depletion or antibody-mediated blockade of pan-integrin αv, or the specific heterodimer αvβ6, in keratinocytes limited epidermal proliferation at the wound edge and prevented re-epithelialization of wounded human organotypic skin both in vivo and in vitro. While we did not observe a migration defect upon αv blockade in vivo, αv was necessary for keratinocyte migration over longer distances in organotypic skin. Integrin αv is required for local activation of latent TGFβ, and the wound healing defect in the setting of integrin αv loss was rescued by exogenous, active TGFβ, indicating that the αv-TGFβ signaling axis is a critical component of the normal epidermal wound healing program. As chronic wounds are associated with decreased TGFβ signaling, restoration of TGFβ activity may have therapeutic utility in some clinical settings.

SUBMITTER: Duperret EK

PROVIDER: S-EPMC4968969 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing.

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Setd2 Epidermal Deficiency Promotes Cutaneous Wound Healing via Activation of AKT/mTOR Signaling

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-25 | GSE163861 | GEO

Integrin αV is a prognostic marker for cutaneous squamous cell carcinoma relapse

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