The effects of the mechanical stretch on human dermal fibroblasts

Abstract

Mechanical force plays a significant role in scar development which is supported by the fact that many high stretching tension areas tend to be keloids or hypertrophic scars. Furthermore, mechanical tension activates resting fibroblasts into activated phenotype which have the features of proliferation and matrix synthesis, and mechanical force has been shown to stimulate the transformation of dermal fibroblast into myofibroblasts, which is one of the important key mediators of fibrosis. Therefore, we aimed to examine the effects of mechanical stretch on proteins expressed in human dermal fibroblasts (HDFs) using proteomics to find out the differences in expression of the proteins according to the presence or absence of stretching.

To generate the mechanical stretch, we made a mechanical cell stimulation machine which has a vacuum induced programmable biostretching system. The device applied multidirectional stretch and it was possible to control real-time manipulation to the attached cells. The mechanical stretch was applied to HDFs 2 hours per day for 3 days. Proteomics analysis was performed to compare the protein expressions between stretched HDFs and non-stretched HDFs.

After mechanical stretch, proliferation of HDFs was significantly increased than non-stretched HDFs. Proteomic analysis using TMT-labeling was performed to find altered protein expression after stretching and a total of 27 proteins showed significantly different expression between study and control groups. Among these proteins, 16 proteins were upregulated and 11 proteins were downregulated.

In the future, validating study will be needed for functional verification of each protein and evaluating the association with the pathway of keloid development and a better understanding of the effects of mechanical stretch on human fibroblasts will help the development of novel technologies that can prevent or reduce pathological scar formation in the future.