Transforming growth factor-beta3 affects plasminogen activator inhibitor-1 expression in fetal mice and modulates fibroblast-mediated collagen gel contraction.
For over two decades, the precise role of transforming growth factor-beta (TGF-beta) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-beta3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-beta downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-beta3 and PAI-1 was investigated using embryonic day 14.5 TGF-beta3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-beta3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell-matrix interaction. These findings provide a further avenue for the interactive role of TGF-beta3 and PAI-1 during fetal scarless repair.
Li
Wai-Yee
WY
Department of Surgery, The Saban Research Institute of Childrens Hospital, Los Angeles, California 90027, USA.
Huang
Eunice Y
EY
Dudas
Marek
M
Kaartinen
Vesa
V
Warburton
David
D
Tuan
Tai-Lan
TL
D000818:Animals; D002921:Cicatrix / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005782:Gels; D051379:Mice; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011247:Pregnancy; D049188:Prenatal Injuries; D053782:Transforming Growth Factor beta3 / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D005782:Gels; D017395:Plasminogen Activator Inhibitor 1; D053782:Transforming Growth Factor beta3; D003094:Collagen