Mechanical strain alters gene expression in an in vitro model of hypertrophic scarring.
Fibroblasts represent a highly mechanoresponsive cell type known to play key roles in normal and pathologic processes such as wound healing, joint contracture, and hypertrophic scarring. In this study, we used a novel fibroblast-populated collagen lattice (FPCL) isometric tension model, allowing us to apply graded biaxial loads to dermal fibroblasts in a 3-dimensional matrix. Cell morphology demonstrated dose-dependent transition from round cells lacking stress fibers in nonloaded lattices to a broad, elongated morphology with prominent actin stress fibers in 800-mg-loaded lattices. Using quantitative real-time RT-PCR, a dose dependent induction of both collagen-1 and collagen-3 mRNA up to 2.8- and 3-fold, respectively, as well as a 2.5-fold induction of MMP-1 (collagenase) over unloaded FPCLs was observed. Quantitative expression of the proapoptotic gene Bax was down-regulated over 4-fold in mechanically strained FPCLs. These results suggest that mechanical strain up-regulates matrix remodeling genes and down-regulates normal cellular apoptosis, resulting in more cells, each of which produces more matrix. This "double burden" may underlie the pathophysiology of hypertrophic scars and other fibrotic processes in vivo.
Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, NY 10016, USA.
Christopher A
CA
Derderian
Nicholas
N
Bastidas
Oren Z
OZ
Lerman
Kirit A
KA
Bhatt
Shin-E
SE
Lin
Jeremy
J
Voss
Jeffrey W
JW
Holmes
Jamie P
JP
Levine
Geoffrey C
GC
Gurtner
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000235:genetics*; D003094:Collagen; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical
D003094:Collagen; D020781:Matrix Metalloproteinase 1