The novel cytokine p43 stimulates dermal fibroblast proliferation and wound repair.
The multifunctional cytokine p43 acts on endothelial and immune cells to control angiogenesis and inflammation. In this report, we describe an additional activity of p43 that specifically promotes fibroblast proliferation and wound repair. In skin wound regions from mice, tumor necrosis factor-alpha induced p43 expression and secretion from macrophages recruited to the site. p43 also promoted fibroblast proliferation through its 146-amino acid N-terminal domain as revealed by deletion mapping. This p43-induced fibroblast proliferation was mediated by extracellular signal-regulated kinase (Erk). Depletion of endogenous p43 in mice by gene disruption retarded wound repair, whereas exogenous supplementation of recombinant human p43 to the wound area stimulated dermal fibroblast proliferation, collagen production, and wound closure. Thus, we have identified a novel p43 activity involving the stimulation of fibroblast proliferation, which could be applied therapeutically to aid wound repair.
Park
Sang Gyu
SG
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, Korea.
Shin
Hyosook
H
Shin
Young Kee
YK
Lee
Yeonsook
Y
Choi
Eung-Chil
EC
Park
Bum-Joon
BJ
Kim
Sunghoon
S
D000818:Animals; D001710:Biotin / Q000737:chemistry; D019921:Biotinylation; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D017353:Gene Deletion; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019394:Ki-67 Antigen / Q000096:biosynthesis; D048670:MAP Kinase Kinase 4; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha; D014945:Wound Healing
D016207:Cytokines; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; C077219:small inducible cytokine subfamily E, member 1; D001710:Biotin; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases