ISSN:
1524-475X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
It has been known for several decades that early gestational human fetuses will regenerate cutaneous wounds resulting in a scarless repair. In postnatal humans, myofibroblasts are known to play a central role in wound healing and in the pathology of fibrosis. The role of the profibrotic growth factor TGF-β1 in human fetal fibroblasts remains unclear, with recent data now showing that TGF-β1 is present in fetal wounds but for shorter periods. We have therefore examined the effects of TGF-β1 on fibroblasts isolated from early human fetuses (〈14week EGA). We have identified that stimulation with 5 ng/ml TGF-β1 induces a significant proportion of human fetal fibroblasts to differentiate into myofibroblasts (approximately 40%), as identified by staining of α-smooth muscle actin (n = 5). Interestingly, this response was earlier (peaking at day 2–3) and more transitory (over by day 4–5) than that seen with postnatal dermal fibroblasts (peaking at day 6–8 and dropping at day 10). We examined the effects of blocking various intracellular pathways involved in TGF-β1 signalling. The early and transitory myofibroblast induction seen in fetal cells is blocked by an inhibitor of p-JNK (n = 4; p =〈 0.05). In contrast, the later and more prolonged induction of myofibroblasts seen in postnatal cells was not affected by inhibition of p-JNK. Despite the fact that fetal fibroblasts do indeed differentiate into myofibroblasts they were further shown to exhibit differential behavior to postnatal myofibroblasts with respect to TGF-β1 stimulation of collagen expression, producing significantly less soluble collagen (approximately 50%, n = 4) after 24 or 48 hours of treatment with TGF-β1 in serum-free media. These results appear to indicate a role for TGF-β1 during cutaneous wound healing in the early fetus and show that the response of fetal cells to this important profibrotic cytokine is rapid and more controlled, being short lived. It is possible that a prolonged response to this cytokine may lead to the overblown nature of postnatal wound healing, resulting in fibrosis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1067-1927.2005.130117w.x
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