The Canadian Institute of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, ON N6A 5C1, Canada.
J Cell Sci. 2010 Nov 1;123(Pt 21):3674-82. doi: 10.1242/jcs.070672. Epub 2010 Oct 12.
In tissue repair, fibroblasts migrate into the wound to produce and remodel extracellular matrix (ECM). Integrins are believed to be crucial for tissue repair, but their tissue-specific role in this process is poorly understood. Here, we show that mice containing a fibroblast-specific deletion of integrin β1 exhibit delayed cutaneous wound closure and less granulation tissue formation, including reduced production of new ECM and reduced expression of α-smooth muscle actin (α-SMA). Integrin-β1-deficient fibroblasts showed reduced expression of type I collagen and connective tissue growth factor, and failed to differentiate into myofibroblasts as a result of reduced α-SMA stress fiber formation. Loss of integrin β1 in adult fibroblasts reduced their ability to adhere to, to spread on and to contract ECM. Within stressed collagen matrices, integrin-β1-deficient fibroblasts showed reduced activation of latent TGFβ. Addition of active TGFβ alleviated the phenotype of integrin-β1-deficient mice. Thus integrin β1 is essential for normal wound healing, where it acts, at least in part, through a TGFβ-dependent mechanism in vivo.
在组织修复中，成纤维细胞迁移到伤口中，以产生和重塑细胞外基质（ECM）。整合素被认为对组织修复至关重要，但它们在这个过程中的组织特异性作用还知之甚少。在这里，我们发现成纤维细胞特异性缺失整合素β1 的小鼠表现出皮肤伤口闭合延迟和肉芽组织形成减少，包括新 ECM 的产生减少和α-平滑肌肌动蛋白（α-SMA）的表达减少。整合素-β1 缺陷型成纤维细胞表现出 I 型胶原和结缔组织生长因子表达减少，并且由于 α-SMA 应激纤维形成减少而无法分化为肌成纤维细胞。成纤维细胞中整合素β1 的缺失降低了它们对 ECM 的黏附、扩展和收缩能力。在受应力的胶原基质中，整合素-β1 缺陷型成纤维细胞中潜伏 TGFβ 的激活减少。添加活性 TGFβ 可缓解整合素-β1 缺陷型小鼠的表型。因此，整合素β1 对于正常的伤口愈合是必不可少的，它至少部分通过体内 TGFβ 依赖的机制发挥作用。
