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Complex epithelial–mesenchymal interactions modulate transforming growth factor‐β expression in keloid‐derived cells
Author(s) -
Xia Wei,
Phan ToanThang,
Lim Ivor J.,
Longaker Michael T.,
Yang George P.
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.012507.x
Subject(s) - keloid , keratinocyte , transforming growth factor , paracrine signalling , fibroblast , wound healing , hacat , transforming growth factor beta , growth factor , cancer research , chemistry , connective tissue , microbiology and biotechnology , receptor , biology , immunology , cell culture , medicine , pathology , biochemistry , genetics
Keloids are proliferative dermal growths representing a pathologic wound healing response. We have previously demonstrated that coculture of fibroblasts derived from either keloid or normal skin have an elevated proliferation rate when cocultured with keloid‐derived keratinocytes vs. normal keratinocytes. In these studies, we examined the contribution of transforming growth factor‐β (TGF‐β) to this phenomenon using a two‐chamber coculture system. Fibroblast proliferation in coculture was slower with the addition of a pan‐TGF‐β neutralizing antibody. Keloid keratinocytes in coculture expressed more TGF‐β1, ‐β3, and TGF‐β receptor 1 than normal keratinocytes. Keloid fibroblasts cocultured with keloid keratinocytes expressed more mRNA for TGF‐β1, ‐β2, TGF‐β receptor 1, and Smad2. Keloid fibroblasts also produced more type I collagen, connective tissue growth factor, and insulin‐like growth factor‐II/mannose‐6‐phosphate receptor when cocultured with keloid keratinocytes vs. normal keratinocytes. Levels of total and activated TGF‐β activity increased when fibroblasts were cocultured with keratinocytes, correlating with the changes in transcriptional activity of TGF‐β. In conclusion, we find a complex paracrine interaction regulates TGF‐β mRNA expression and activation between keratinocytes and fibroblasts. These data suggest that keloid pathogenesis may result from both an increased TGF‐β production and activation by the keloid keratinocyte, and elevated TGF‐β expression, utilization, and signaling in keloid fibroblasts.