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Skin equivalent tensional force alters keloid fibroblast behavior and phenotype
Author(s) -
Suarez Edna,
Syed Farhatullah,
Rasgado Teresa A.,
Walmsley Alan,
Mandal Parthasarathi,
Bayat Ardeshir
Publication year - 2014
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/wrr.12215
Subject(s) - keloid , gene knockdown , fibroblast , skin equivalent , extracellular matrix , in vivo , chemistry , wound healing , microbiology and biotechnology , tension (geology) , anatomy , in vitro , pathology , biology , gene , immunology , medicine , materials science , genetics , biochemistry , ultimate tensile strength , keratinocyte , metallurgy
Skin tension may influence keloid scar behavior, development, and spreading, e.g., butterfly‐shaped keloid disease in the sternum. Here, we developed a three‐dimensional (3 D ) in vitro model to mimic in vivo tension and evaluate keloid fibroblast ( KF ) behavior and extracellular matrix synthesis under tension. In vivo skin tension measured in volunteers ( n = 4) using 3 D image photogrammetry enabled prediction of actual force (35 mN). A novel cell force monitor applied tension in a fibroblast‐populated 3 D collagen lattice replicating the in vivo force. The effect of tension on keloid ( n = 10) fibroblast (KF) and normal skin ( n = 10) fibroblasts ( NF ) at set time points (6, 12, and 24 hours) was measured in Hsp27 , PAI‐2 , and α2β1 integrin, tension‐related genes demonstrating significant ( p < 0.05) time‐dependent regulation of these genes in NF vs. KF with and without tension. KF showed higher ( p < 0.05) proliferation post‐tension. Knockdown of all three genes in 24 and 48 hours with and without tension showed significant down‐regulation in NF vs. KF . Additionally, we show significant ( p < 0.05) modification of the expression of extracellular matrix‐related genes post‐tension following down‐regulation of Hsp27 , PAI‐2 , or α2β1 integrin. Finally, we demonstrate significant alteration in NF compared with KF morphology following knockdown. In conclusion, this study shows induction of tension‐related genes expression following mechano‐regulation in KF s, with potential relevance to its development and therapy.