Biomechanics Research Today is a free monthly online journal that collates and summarizes the latest research about Biomechanics, including details on mechanics of living organisms, movement, locomotion, prosthetic limbs.

Increased transcriptional response to mechanical strain in keloid fibroblasts due to increased focal adhesion complex formation.

Wang Z, Fong KD, Phan TT, Lim IJ, Longaker MT, Yang GP

Department of Surgery, Stanford University Medical School, Stanford 94305, and Palo Alto VA Health Care System, California, USA.

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-beta isoforms and collagen Ialpha, genes differentially expressed in keloids. Keloid fibroblasts produced more mRNA for TGF-beta1, TGF-beta2, and collagen Ialpha 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 beta1, 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.

Published 5 December 2005 in J Cell Physiol, 206(2): 510-7.
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