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The altered mechanical phenotype of fetal fibroblasts hinders myofibroblast differentiation
Author(s) -
Jerrell Rachel J.,
Leih Mitchell J.,
Parekh Aron
Publication year - 2018
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.12677
Subject(s) - myofibroblast , extracellular matrix , dermis , microbiology and biotechnology , wound healing , fetus , fibroblast , transforming growth factor , extracellular , growth factor , phenotype , chemistry , pathology , anatomy , biology , immunology , fibrosis , medicine , in vitro , biochemistry , genetics , pregnancy , receptor , gene
During the dermal wound healing process, the mechanical rigidity of the newly deposited extracellular matrix and transforming growth factor‐β1 promote the transition of fibroblasts into myofibroblasts. Myofibroblasts generate large cellular forces that contract and remodel the extracellular matrix leading to scar formation. In contrast, myofibroblasts are not detected in fetal dermal wounds which are more compliant and contain less transforming growth factor‐β1 than adult wounds. Instead, fetal fibroblasts orchestrate scarless healing of dermal wounds resulting in healed tissues that resemble uninjured dermis. While these biomechanical differences suggest that the fetal wound environment promotes smaller cellular forces which enable regeneration, previous studies indicate that fetal fibroblasts have unique contractile properties that may facilitate scarless dermal repair. Therefore, we tested whether physiologic wound rigidities and transforming growth factor‐β1 induce contractile forces and myofibroblast differentiation of fetal dermal fibroblasts. In comparison to their adult dermal counterparts, we found that fetal fibroblasts exhibit a deficient contractile response to rigid extracellular matrix and transforming growth factor‐β1. Our data suggest that the contractile phenotype of fetal dermal fibroblasts limits their cellular force production and prevents their ability to differentiate into myofibroblasts.