Differential expression and regulation of extracellular matrix-associated genes in fetal and neonatal fibroblasts.
Adults and neonates heal wounds by a repair process associated with scarring in contrast to scar-free wound healing in the fetus. In the present study, human dermal fetal fibroblasts, representing the scarless phenotype, and neonatal human dermal fibroblasts, representing scar-forming phenotype, were examined for potential differences that might influence the wound healing process. Fetal fibroblasts secreted four- to tenfold more latent transforming growth factor-beta1 depending on the cell strains compared. Fetal fibroblasts also produced higher levels of collagen protein and mRNA for most types of collagen (particularly type III) as compared to neonatal cells. Interestingly, mRNA for type V collagen was significantly reduced in fetal cells. Neonatal fibroblasts expressed significantly higher levels of latent transforming growth factor-beta1 binding protein mRNA, in contrast to almost undetectable levels in fetal fibroblasts. By ligand blot analysis, the levels of insulin-like growth factor binding protein-3, a reported mediator of transforming growth factor-beta1 activity, was eightfold higher in neonatal versus fetal fibroblasts. Approximately 20 other mRNAs for various cytokines, matrix molecules and receptors were examined and found to be similar between the two cell types. The phenotypic differences described in this article may represent potentially important mechanisms to explain the differences in the quality of wound repair observed in fetal versus adult/neonatal tissues.
Gosiewska
A
A
Johnson & Johnson Wound Healing Technology Resource Center, Skillman, New Jersey 08558-9418, USA. agosiew@cpus.jnj.com
Yi
C F
CF
Brown
L J
LJ
Cullen
B
B
Silcock
D
D
Geesin
J C
JC
D000367:Age Factors; D002460:Cell Line; D002921:Cicatrix / Q000209:etiology / Q000503:physiopathology; D003094:Collagen / Q000502:physiology; D005109:Extracellular Matrix / Q000235:genetics* / Q000502:physiology*; D005333:Fetus; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology; D012333:RNA, Messenger / Q000502:physiology; D012867:Skin / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology*
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen