A role for TGF-beta1-induced cellular responses during wound healing of the non-scarring early human fetus?
Early human fetuses regenerate cutaneous wounds perfectly without scarring. However, transforming growth factor-beta1 (TGF-beta1), the cytokine linked with scarring in mature tissue, is also present during fetal wound repair, albeit transiently. We present a comparison of response to TGF-beta1 by fibroblasts derived from early human fetal skin (non-scarring) and their mature (scarring) postnatal counterparts, which revealed that although fetal fibroblasts do indeed differentiate into myofibroblasts, this response is altogether more rapid and short-lived. Fetal fibroblasts also failed to exhibit the TGF-beta1-induced increase in collagen (mRNA and protein) demonstrated by their postnatal counterparts. Fetal cells exhibited a comparatively short-lived or rapid phosphorylation of several components of the TGF-beta1 signaling pathways: Smad2/3 and c-Jun N-terminal kinase. Unlike quiescent postnatal fibroblasts, quiescent fetal fibroblasts also phosphorylated extracellular signal-regulated kinases in response to TGF-beta1. These altered responses to TGF-beta1 may well contribute to the transition between perfect regeneration and scar formation seen during development.
RAFT Institute of Plastic Surgery, Leopold Muller Building, Mount Vernon Hospital, Northwood Middlesex, UK. rolfek@raft.ac.uk
Kerstin J
KJ
Rolfe
Janette
J
Richardson
Charlotte
C
Vigor
Laurie M
LM
Irvine
Addie O
AO
Grobbelaar
Claire
C
Linge
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D005333:Fetus / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D024042:Collagen Type I; D012333:RNA, Messenger; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D048031:JNK Mitogen-Activated Protein Kinases