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Increased transcriptional response to mechanical strain in keloid fibroblasts due to increased focal adhesion complex formation
Author(s) -
Wang Zhen,
Fong Kenton D.,
Phan ToanThang,
Lim Ivor J.,
Longaker Michael T.,
Yang George P.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20486
Subject(s) - keloid , focal adhesion , fibroblast , chemistry , wound healing , microbiology and biotechnology , kinase , vinculin , signal transduction , biology , pathology , immunology , medicine , biochemistry , in vitro
Clinicians have observed that keloids preferentially form in body areas subject to increased skin tension. We hypothesized a difference exists in the transcriptional response of keloid fibroblasts to mechanical strain compared with normal fibroblasts. Normal and keloid fibroblasts were seeded in a device calibrated to deliver a known level of equibiaxial strain. We examined the transcriptional response of TGF‐β isoforms and collagen Iα, genes differentially expressed in keloids. Keloid fibroblasts produced more mRNA for TGF‐β1, TGF‐β2, and collagen Iα after mechanical strain compared to normals, and this was correlated with protein production. Inhibiting the major mechanical signal transduction pathway with the ERK inhibitor, U0126, blocked upregulation of gene expression. In addition, keloid fibroblasts formed more focal adhesion complexes as measured by immunofluorescence for focal adhesion kinase, integrin β1, and vinculin. Finally, there is increased activation of focal adhesion kinase when we detected the phosphorylated form of focal adhesion kinase with immunofluorescence and immunoblotting. In summary, keloid fibroblasts have an exaggerated response to mechanical strain compared to normal fibroblasts leading to increased production of pro‐fibrotic growth factors. This may be one molecular mechanism for the development of keloids. J. Cell. Physiol. 206: 510–517, 2006. © 2005 Wiley‐Liss, Inc.

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