Premium
Transforming growth factor‐β 3 affects plasminogen activator inhibitor‐1 expression in fetal mice and modulates fibroblast‐mediated collagen gel contraction
Author(s) -
Li WaiYee,
Huang Eunice Y.,
Dudas Marek,
Kaartinen Vesa,
Warburton David,
Tuan TaiLan
Publication year - 2006
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/j.1743-6109.2006.00158.x
Subject(s) - dermis , plasminogen activator , plasminogen activator inhibitor 1 , transforming growth factor , fibroblast , fetus , microbiology and biotechnology , knockout mouse , fibrosis , chemistry , activator (genetics) , contraction (grammar) , endocrinology , medicine , biology , anatomy , in vitro , biochemistry , gene , pregnancy , genetics
For over two decades, the precise role of transforming growth factor‐β (TGF‐β) 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‐β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor‐1 (PAI‐1), a known TGF‐β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF‐β3 and PAI‐1 was investigated using embryonic day 14.5 TGF‐β3 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‐β3 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‐β3 and PAI‐1 during fetal scarless repair.