Delayed wound healing and epidermal hyperproliferation in mice lacking JunB in the skin
Delayed wound healing and epidermal hyperproliferation in mice lacking JunB in the skin
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DOI：
10.1038/sj.jid.5700123
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发表时间：
2006-04-01
影响因子：
6.5
通讯作者：
Angel, Peter
中科院分区：
文献类型：
--
作者：
Florin, Lore;Knebel, Julia;Angel, Peter
皮肤对损伤和应激的反应包括表皮增殖和分化之间的平衡的暂时变化以及免疫系统的激活。可溶性因子通过协调角质形成细胞、成纤维细胞和炎性细胞之间的细胞间通讯在这些复杂过程的调节中起重要作用。在这项研究中，我们证明，JunB，激活蛋白-1转录因子家族的成员，是一个重要的调节细胞因子的表达，从而在皮肤损伤和应激反应的关键参与。皮肤中缺乏JunB的小鼠发育正常，表明JunB既不是皮肤器官形成所需的，也不是体内平衡所需的。然而，在创伤和用佛波酯12-O-癸酰基-佛波醇-13-乙酸酯治疗后，皮肤中的JunB-缺乏同样导致明显的表皮过度增殖、分化紊乱和炎症延长。此外，在伤口愈合期间观察到延迟的组织重塑。这些表型皮肤异常与JunB依赖性的表达水平改变和伤口修复的重要介质的动力学相关，如皮肤真皮和表皮区室中的粒细胞巨噬细胞集落刺激因子、生长调节蛋白-1、巨噬细胞炎性蛋白-2和脂质运载蛋白-2，以及体外突变真皮成纤维细胞伤口收缩能力降低。
The cutaneous response to injury and stress comprises a temporary change in the balance between epidermal proliferation and differentiation as well as an activation of the immune system. Soluble factors play an important role in the regulation of these complex processes by coordinating the intercellular communication between keratinocytes, fibroblasts, and inflammatory cells. In this study, we demonstrate that JunB, a member of the activator protein-1 transcription factor family, is an important regulator of cytokine expression and thus critically involved in the cutaneous response to injury and stress. Mice lacking JunB in the skin develop normally, indicating that JunB is neither required for cutaneous organogenesis, nor homeostasis. However, upon wounding and treatment with the phorbol ester 12-O-decanoyl-phorbol-13-acetate, JunB-deficiency in the skin likewise resulted in pronounced epidermal hyperproliferation, disturbed differentiation, and prolonged inflammation. Furthermore, delayed tissue remodelling was observed during wound healing. These phenotypic skin abnormalities were associated with JunB-dependent alterations in expression levels and kinetics of important mediators of wound repair, such as granulocyte macrophage colony-stimulating factor, growth-regulated protein-1, macrophage inflammatory protein-2, and lipocalin-2 in both the dermal and epidermal compartment of the skin, and a reduced ability of wound contraction of mutant dermal fibroblasts in vitro.