Impaired cutaneous wound healing with excess granulation tissue formation in TNFα-null mice
Impaired cutaneous wound healing with excess granulation tissue formation in TNFα-null mice
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DOI：
10.1007/s00403-009-0969-z
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发表时间：
2009-08-01
影响因子：
3
通讯作者：
Shinozaki, Masahiro
中科院分区：
文献类型：
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作者：
Shinozaki, Maki;Okada, Yuka;Shinozaki, Masahiro
我们使用肿瘤坏死因子α（TNF α）缺陷小鼠研究了缺乏TNF α对小鼠皮肤伤口愈合过程的影响。在野生型（WT）或TNF α-null（KO）小鼠的背部皮肤中产生直径为5.0 mm的全层圆形皮肤伤口。在特定的愈合间隔后，通过肉眼观察、组织学、免疫组织化学或实时逆转录聚合酶链反应评价愈合模式。还检查了Smad7基因转移对KO小鼠的愈合表型的影响。结果表明，在小鼠背部皮肤的圆形伤口中，TNF α的缺失促进肉芽组织形成并延迟上皮再生。免疫组织化学显示WT和KO小鼠之间新生成的肉芽组织中巨噬细胞和肌成纤维细胞的分布似乎相似。然而，缺乏TNF α增强TGF β 1和胶原I α 2在这样的组织中的mRNA表达。Smad7基因转移抵消了KO小鼠过度肉芽组织形成。总之，缺乏TNF α增强了愈合真皮中Smad介导的纤维化反应，并延缓了愈合小鼠皮肤伤口中的上皮再形成。
We examined the effects of lacking tumor necrosis factor alpha (TNF alpha) on the healing process of a cutaneous wound in mice using TNF alpha-deficient mice. A full-thickness circular cutaneous wound 5.0 mm in diameter was produced in the dorsal skin of wild-type (WT) or TNF alpha-null (KO) mice. After specific intervals of healing, the healing pattern was evaluated by macroscopic observation, histology, immunohistochemistry, or real-time reverse transcription-polymerase chain reaction. Effect of Smad7 gene transfer on the healing phenotype of KO mice was also examined. The results showed that loss of TNF alpha promotes granulation tissue formation and retards reepithelialization in a circular wound in mouse dorsal skin. Immunohistochemistry showed that distribution of macrophages and myofibroblasts in newly generated granulation tissue seemed similar between WT and KO mice. However, lacking TNF alpha enhanced mRNA expression of TGF beta 1 and collagen I alpha 2 in such tissue. Smad7 gene transfer counteracted excess granulation tissue formation in KO mice. In conclusion, lacking TNF alpha potentiates Smad-mediated fibrogenic reaction in healing dermis and retards reepithelialization in a healing mouse cutaneous wound.