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.
Rolfe
Kerstin J
KJ
RAFT Institute of Plastic Surgery, Leopold Muller Building, Mount Vernon Hospital, Northwood Middlesex, UK. rolfek@raft.ac.uk
Richardson
Janette
J
Vigor
Charlotte
C
Irvine
Laurie M
LM
Grobbelaar
Addie O
AO
Linge
Claire
C
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