Department of Dentistry, University of Western Ontario, London, Ontario, Canada.
J Invest Dermatol. 2013 Apr;133(4):899-906. doi: 10.1038/jid.2012.438. Epub 2012 Nov 29.
Integrins are heterodimers that mediate cell attachment to the extracellular matrix. Previously, we used fibroblast-specific knockout mice to show that the integrin β1 subunit was required in vivo for dermal fibrogenesis and cutaneous tissue repair. Here, we show that integrin β1 expression by fibroblasts is required for dermal homeostasis; at 8 weeks after deletion of integrin β1, the dermis is significantly thinner, expressing less collagen and displaying reduced generation of reactive oxygen species (ROS). Cultured integrin β1-deficient fibroblasts show reduced rac1 activation and ROS generation. Overexpressing rac1 in integrin β1-deficient fibroblasts restored ROS generation; adding hydrogen peroxide to integrin β1-deficient fibroblasts restored Col1a2 (collagen, type I, α2) and α-smooth muscle actin (α-SMA) mRNA expression and α-SMA protein expression and stress fiber formation. Thus integrin β1 expression by fibroblasts is required for the maintenance of dermal connective tissue via a rac/ROS pathway.
整合素是介导细胞与细胞外基质附着的异二聚体。先前，我们使用成纤维细胞特异性敲除小鼠表明整合素β1 亚基在体内真皮纤维化和皮肤组织修复中是必需的。在这里，我们表明成纤维细胞的整合素β1 表达对于皮肤稳态是必需的；在整合素β1 缺失 8 周后，真皮明显变薄，胶原蛋白表达减少，并显示活性氧（ROS）生成减少。培养的整合素β1 缺陷型成纤维细胞显示 Rac1 激活和 ROS 生成减少。在整合素β 1 缺陷型成纤维细胞中过表达 Rac1 恢复了 ROS 的生成；向整合素β 1 缺陷型成纤维细胞中添加过氧化氢恢复了 Col1a2（胶原，类型 I，α2）和α-平滑肌肌动蛋白（α-SMA）mRNA 表达以及α-SMA 蛋白表达和应激纤维形成。因此，成纤维细胞的整合素β1 表达通过 rac/ROS 途径维持皮肤结缔组织。
