Wnt-4 expression is increased in fibroblasts after TGF-beta1 stimulation and during fetal and postnatal wound repair.
BACKGROUND
Wnt-4 is a mitogen expressed during postnatal repair and scar formation; however, its expression profile during scarless repair is unknown. Transforming growth factor (TGF)-beta1 has high expression during healing with scar formation. Whether TGF-beta1 directly influences Wnt-4 expression in fetal or postnatal fibroblasts has not been examined.


METHODS
Primary fetal and postnatal mouse fibroblasts were stimulated with TGF-beta1 and Wnt-4 expression quantitated by real-time polymerase chain reaction. Fetal E17 and postnatal mouse excisional wounds were also analyzed for Wnt-4 expression by real-time polymerase chain reaction.


RESULTS
In E17 fibroblasts after TGF-beta1 stimulation, Wnt-4 expression increased 4-fold at 1 hour (p < 0.05) and peaked with an 11-fold increase at 2 hours (p < 0.05). By 24 hours, expression decreased to 2-fold baseline levels (p < 0.05). In postnatal fibroblasts, Wnt-4 expression also increased after TGF-beta stimulation, but peak expression was larger and relatively delayed, with a 17-fold increase at 12 hours (p < 0.005). Expression levels at 24 hours were still 4-fold greater than baseline (p < 0.05). In E17 fetal skin, Wnt-4 expression was 3.5-fold greater compared with 3-week-old mice (p < 0.005). Small increases in Wnt-4 expression (less than 2-fold) occurred during both fetal scarless and postnatal scarring mouse wound repair.


CONCLUSIONS
The authors' data suggest that TGF-beta directly increases Wnt-4 expression in fetal and postnatal fibroblasts and that Wnt-4 is increased in both fetal and postnatal repair.
Colwell
Amy S
AS
Department of Surgery, Division of Plastic Surgery, Children's Surgical Research Program, Stanford, Calif. 94305-5148, USA.
Krummel
Thomas M
TM
Longaker
Michael T
MT
Lorenz
H Peter
HP
D000818:Animals; D002921:Cicatrix / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism*; D007155:Immunologic Factors / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012867:Skin / Q000293:injuries / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D051153:Wnt Proteins / Q000096:biosynthesis*; D060528:Wnt4 Protein; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology; D014947:Wounds and Injuries / Q000378:metabolism
D007155:Immunologic Factors; D011518:Proto-Oncogene Proteins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse