Mutations in the CD18 gene encoding the common β-chain of β2 integrins result in impaired wound healing in humans and mice suffering from leukocyte adhesion deficiency syndrome type 1 (LAD1). Transplantation of adipose tissue-derived mesenchymal stem cells (MSCs) restores normal healing of CD18-/- wounds by restoring the decreased TGF-β1 concentrations. TGF-β1 released from MSCs leads to enhanced myofibroblast differentiation, wound contraction, and vessel formation. We uncover that MSCs are equipped with a sensing mechanism for TGF-β1 concentrations at wound sites. Low TGF-β1 concentrations as occurring in CD18-/- wounds induce TGF-β1 release from MSCs, whereas high TGF-β1 concentrations suppress TGF-β1 production. This regulation depends on TGF-β receptor sensing and is relayed to microRNA-21 (miR-21), which subsequently suppresses the translation of Smad7, the negative regulator of TGF-β1 signaling. Inactivation of TGF-β receptor, or overexpression or silencing of miR-21 or Smad7, abrogates TGF-β1 sensing, and thus prevents the adaptive MSC responses required for tissue repair.

中文翻译：

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MSC通过对低TGF-β1水平的适应性反应来挽救鼠LAD1模型中受损的伤口愈合。

编码β2整合素的公共β链的CD18基因中的突变会导致人类和患有1型白细胞粘连缺乏综合征（LAD1）的小鼠的伤口愈合受损。脂肪组织间充质干细胞（MSCs）的移植通过恢复降低的TGF-β1浓度来恢复CD18-/-伤口的正常愈合。从MSCs释放的TGF-β1导致增强的成肌纤维细胞分化，伤口收缩和血管形成。我们发现，MSC在伤口部位配备了针对TGF-β1浓度的传感机制。在CD18-/-伤口中出现的低TGF-β1浓度会诱导TGF-β1从MSC释放，而高TGF-β1浓度会抑制TGF-β1的产生。此调节取决于TGF-β受体的感应，并转导至microRNA-21（miR-21），随后抑制Tmad-β1信号转导的负调节子Smad7的翻译。TGF-β受体失活，或者miR-21或Smad7的过表达或沉默会废止TGF-β1的感应，从而阻止组织修复所需的适应性MSC反应。