title: Differential gene expression in response to transforming growth factor-beta1 by fetal and postnatal dermal fibroblasts.
abstract: The multipotent growth factor transforming growth factor (TGF)-beta1 is consistently linked with fibrosis and scarring. The perfect (scarless) healing of cutaneous wounds in early gestational age fetuses is proposed to be due to this tissue's predominance of the TGF-beta3 isoform over the profibrotic TGF-beta1 and 2. Nevertheless, TGF-beta1 is present during wound healing in the early fetus and recently we demonstrated that relevant intracellular signaling pathways are activated (albeit transiently) on TGF-beta1 stimulation. This study aimed to determine whether TGF-beta1 has different effects on gene transcription in human fetal (<14 weeks) vs. human postnatal dermal fibroblasts, using real-time polymerase chain reaction. The regulation pattern of a number of TGF-beta response genes differed dramatically between the two cell sources. The typical autocrine loop of TGF-beta1 autoinduction did not occur in fetal fibroblasts and genes that are normally up-regulated, connective tissue growth factor and collagen type I were actually down-regulated. Furthermore, other response genes responded in a delayed fashion (TGF-beta3) compared with that seen in the more developmentally mature postnatal fibroblasts. Finally, genes unaltered by TGF-beta stimulation in postnatal cells, TGF-beta2 and collagen III, were up-regulated in fetal cells. These developmentally related differences in fibroblast response to TGF-beta1 may influence wound-healing outcome, i.e., perfect regeneration or fibrosis.
authors.affiliation: RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood Middlesex, United Kingdom. rolfek@raft.ac.uk
authors.forename: Kerstin J
authors.initials: KJ
authors.lastname: Rolfe
authors.forename: Laurie M
authors.initials: LM
authors.lastname: Irvine
authors.forename: Addie O
authors.initials: AO
authors.lastname: Grobbelaar
authors.forename: Claire
authors.initials: C
authors.lastname: Linge
mesh_terms: D015153:Blotting, Western; 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; D005260:Female; D005333:Fetus / Q000166:cytology* / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D048031:JNK Mitogen-Activated Protein Kinases