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首页> 外文期刊>Cell cycle >The integrin v-TGF signaling axis is necessary for epidermal proliferation during cutaneous wound healing
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The integrin v-TGF signaling axis is necessary for epidermal proliferation during cutaneous wound healing

机译：整联蛋白v-TGF信号转导轴是皮肤伤口愈合过程中表皮增生所必需的

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摘要

Proliferation and migration of epidermal keratinocytes are essential for proper cutaneous wound closure after injury. v integrins and several of their ligandsvitronectin, TGF and thrombospondinare up-regulated in healing wounds. However, the role of v integrins in wound re-epithelialization is unknown. Here, we show that genetic depletion or antibody-mediated blockade of pan-integrin v, or the specific heterodimer v6, 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 v blockade in vivo, v was necessary for keratinocyte migration over longer distances in organotypic skin. Integrin v is required for local activation of latent TGF, and the wound healing defect in the setting of integrin v loss was rescued by exogenous, active TGF, indicating that the v-TGF signaling axis is a critical component of the normal epidermal wound healing program. As chronic wounds are associated with decreased TGF signaling, restoration of TGF activity may have therapeutic utility in some clinical settings.
机译：表皮角质形成细胞的增殖和迁移对于受伤后适当的皮肤伤口闭合至关重要。 v整联蛋白及其一些配体在创面愈合中上调了维tronectin，TGF和血小板反应蛋白。然而，整合素在伤口上皮形成中的作用尚不清楚。在这里，我们显示了角质形成细胞中泛整合素v或特定异二聚体v6的遗传耗竭或抗体介导的阻滞限制了伤口边缘的表皮增殖，并在体内和体外均阻止了受伤的人类器官型皮肤的重新上皮形成。虽然我们没有观察到体内v阻断后的迁移缺陷，但v对于角型细胞在器官型皮肤中更长距离的迁移是必需的。整合素v是潜在TGF的局部活化所必需的，而整合素v丢失的伤口愈合缺陷可通过外源性活性TGF来挽救，这表明v-TGF信号轴是正常表皮伤口愈合程序的关键组成部分。由于慢性伤口与TGF信号转导降低有关，因此TGF活性的恢复在某些临床环境中可能具有治疗作用。

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