Cutaneous scarring: Modulation by transforming growth factor-beta and its antagonists
Başlık:
Cutaneous scarring: Modulation by transforming growth factor-beta and its antagonists
Yazar:
Shah, Mamta, author.
ISBN:
9780355978520
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (426 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
Cutaneous wounds in early fetal life heal without scar formation while wound healing in post-natal life is characterised by scar formation (Whitby and Ferguson, 1991a). The growth factor profiles of adult and fetal healing wounds differ. Whitby and Ferguson (1991b) could not immunolocalise Transforming growth factor-beta (TGF-beta) or basic Fibroblast growth factor (bFGF) in fetal mouse lip wounds whilst both were present in neonatal and adult lip wounds. This project investigated the effects of manipulating the growth factor profile of healing adult wounds on scar formation. In particular, the Transforming growth factor-beta profile of incisional, cutaneous wounds in adult rodents was experimentally manipulated by exogenous addition of neutralising antibodies to TGF-beta1,2&3, or of the TGF-beta isoforms themselves.This study has shown that early addition of neutralising antibody to TGF-beta1,2 to incisional wounds alters the architecture of the neodermis to resemble that of the normal dermis and reduces scarring. During the early stages of wound healing, exogenous addition of neutralising antibody to TGF-beta1,2 reduces the inflammatory and angiogenic responses and reduces the deposition of the extracellular matrix without, however, altering the tensile strength of the wounds. Using isoform specific antibodies, it was shown that exogenous addition of neutralising antibody to TGF-beta1, alone had some effect in reducing scarring while neutralising antibody to TGF-beta 2 alone did not reduce scarring. However exogenous addition of neutralising antibody to TGF-beta1, plus neutralising antibody to TGF-beta2 together, markedly altered the architecture of the neodermis and reduced scarring thereby implicating both TGF-beta1 and TGF-beta2 in scar formation. Exogenous addition of TGF-beta3 to incisional wounds also altered the architecture of the neodermis and reduced scarring. Exogenous addition of TGF-beta3 reduced the inflammatory response and extracelluar matrix during the early stages of wound healing and altered the architecture of the neodermis to resemble that of the normal skin. By contrast, exogenous addition of TGF-beta1, or TGF-beta2 to incisional wounds transiently increased extracellular matrix deposition during the early stages of wound healing without altering the ultimate scar formation. Immunohistochemical studies showed that wounds treated with either TGF-beta3 or with the neutralising antibodies to TGF-beta1+2 had less immunoreactive TGF-beta1, and TGF-beta2 and more TGF-beta3 during the first week of healing compared with the control wounds. These wounds also appeared to have less immunoreactive Platelet derived growth factor (PDGF) B-chain and basic Fibroblast growth factor (FGF) compared with the control wounds. Concomitant administration of TGF-beta3 and neutralising antibodies to TGF-beta1+2 to incisional wounds also reduced the inflammatory response, extracellular matrix deposition during the early stages of wound healing and altered the architecture of the neodermis and reduced scarring. However these effects were not better than either treatment alone. This project has demonstrated that scarless healing is not unique to fetal life. Early manipulation of the TGF-beta profile of adult wounds by lowering TGF-beta1, and TGF-beta2 relative to TGF-beta3 using neutralising antibodies to TGF-beta1+2 or TGF-beta3 can reduce scarring in post-natal life. This study suggests a novel therapeutic approach of reducing scar formation in post-natal life and is therefore of great clinical relevance.
Notlar:
School code: 1543
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(683888.1) | 683888-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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