Impaired cutaneous wound healing with excess granulation tissue formation in TNFalpha-null mice.
We examined the effects of lacking tumor necrosis factor alpha (TNFalpha) on the healing process of a cutaneous wound in mice using TNFalpha-deficient mice. A full-thickness circular cutaneous wound 5.0 mm in diameter was produced in the dorsal skin of wild-type (WT) or TNFalpha-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 TNFalpha 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 TNFalpha enhanced mRNA expression of TGFbeta1 and collagen Ialpha2 in such tissue. Smad7 gene transfer counteracted excess granulation tissue formation in KO mice. In conclusion, lacking TNFalpha potentiates Smad-mediated fibrogenic reaction in healing dermis and retards reepithelialization in a healing mouse cutaneous wound.
Shinozaki
Maki
M
Department of Critical Care Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan. shinop@wakayama-med.ac.jp
Okada
Yuka
Y
Kitano
Ai
A
Ikeda
Kazuo
K
Saika
Shizuya
S
Shinozaki
Masahiro
M
D000818:Animals; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000276:immunology* / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D006097:Granulation Tissue / Q000276:immunology* / Q000473:pathology; D006099:Granuloma / Q000276:immunology; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000254:growth & development / Q000276:immunology* / Q000473:pathology; D051906:Smad7 Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
D024042:Collagen Type I; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha