Pullar Christine E, Isseroff R Rivkah
Department of Dermatology, University of California, Davis, TB 192, One Shields Avenue, CA 95616, USA.
J Cell Sci. 2006 Feb 1;119(Pt 3):592-602. doi: 10.1242/jcs.02772.
Dermal fibroblasts are required for skin wound repair; they migrate into the wound bed, proliferate, synthesize extracellular matrix components and contract the wound. Although fibroblasts express beta2-adrenergic receptors (beta2-AR) and cutaneous keratinocytes can synthesize beta-AR agonists (catecholamines), the functional significance of this hormonal mediator network in the skin has not been addressed. Emerging studies from our laboratory demonstrate that beta2-AR activation modulates keratinocyte migration, essential for wound re-epithelialization. Here we describe an investigation of the effects of beta2-AR activation on the dermal component of wound healing. We examined beta2-AR-mediated regulation of biological processes in dermal fibroblasts that are critical for wound repair: migration, proliferation, contractile ability and cytoskeletal conformation. We provide evidence for the activation of at least two divergent beta2-AR-mediated signaling pathways in dermal fibroblasts, a Src-dependent pro-migratory pathway, transduced through the epidermal growth factor receptor and extracellular signal-regulated kinase, and a PKA-dependent pro-proliferative pathway. beta2-AR activation attenuates collagen gel contraction and alters the actin cytoskeleton and focal adhesion distribution through PKA-dependent mechanisms. Our work uncovers a previously unrecognized role for the adrenergic hormonal mediator network in the cutaneous wound repair process. Exploiting these divergent beta2-AR agonist responses in cutaneous cells may generate novel therapeutic approaches for the control of wound healing.
皮肤伤口修复需要真皮成纤维细胞；它们迁移到伤口床，增殖，合成细胞外基质成分并收缩伤口。虽然成纤维细胞表达β2 - 肾上腺素能受体（β2 - AR），且皮肤角质形成细胞能合成β - AR激动剂（儿茶酚胺），但该激素介导网络在皮肤中的功能意义尚未得到探讨。我们实验室的新研究表明，β2 - AR激活可调节角质形成细胞迁移，这对伤口再上皮化至关重要。在此，我们描述了一项关于β2 - AR激活对伤口愈合真皮成分影响的研究。我们研究了β2 - AR介导的对真皮成纤维细胞中对伤口修复至关重要的生物学过程的调节：迁移、增殖、收缩能力和细胞骨架构象。我们提供证据表明，真皮成纤维细胞中至少有两条不同的β2 - AR介导的信号通路被激活，一条是通过表皮生长因子受体和细胞外信号调节激酶转导的Src依赖性促迁移通路，另一条是PKA依赖性促增殖通路。β2 - AR激活通过PKA依赖性机制减弱胶原凝胶收缩，并改变肌动蛋白细胞骨架和粘着斑分布。我们的工作揭示了肾上腺素能激素介导网络在皮肤伤口修复过程中以前未被认识的作用。利用皮肤细胞中这些不同的β2 - AR激动剂反应可能会产生控制伤口愈合的新治疗方法。
