Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration

被引:206
作者
Mori, R
Kondo, T
Ohshima, T
Ishida, Y
Mukaida, N
机构
[1] Kanazawa Univ, Grad Sch Med Sci, Div Environm Sci Forens & Social Environm Med, Kanazawa, Ishikawa 9208640, Japan
[2] Kanazawa Univ, Canc Res Inst, Div Mol Bioregulat, Kanazawa, Ishikawa 920, Japan
关键词
TNF-Rp55; angiogenesis; collagen production;
D O I
10.1096/fj.01-0776com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To clarify biological roles of tumor necrosis factor receptor p55 (TNF-Rp55)-mediated signals in wound healing, skin excisions were prepared in BALB/c (WT) and TNF-Rp55-deficient (KO) mice. In WT mice, the wound area was reduced to 50% of the original area 6 days after injury, with angiogenesis and collagen accumulation. Histopathologically, reepithelialization rate was similar to80% 6 days. Myeloperoxidase activity and macrophage recruitment were the most evident 1 and 6 days after injury, respectively. Gene expression of adhesion molecules, interleukin 1alpha (IL-1alpha), IL-1beta, monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-2, transforming growth factor beta1 (TGF-beta1) connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), Flt-1, and Flk-1 was enhanced at the wound site. In KO mice, an enhancement in angiogenesis, collagen content, and reepithelialization was accelerated with the increased gene expression of TGF-beta1, CTGF, VEGF, Flt-1, and Flk-1 at the wound sites, resulting in accelerated wound healing compared with WT mice. In contrast, leukocyte infiltration, mRNA expression of adhesion molecules, and cytokines were significantly reduced in KO mice. These observations suggest that TNF-Rp55-mediated signals have some role in promoting leukocyte infiltration at the wound site and negatively affect wound healing, probably by reducing angiogenesis and collagen accumulation.
引用
收藏
页码:963 / 974
页数:12
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