Int J Burn Trauma 2012;2(1):18-28
Review Article
The role of the TGF-Beta family in wound healing, burns and scarring, a review
Jack W Penn, Adriaan O Grobbelaar, Kerstin J Rolfe
The Institute of Plastic Surgery, Research and Education. Dept Plastic Surgery, The Royal Free Hospital, Pond St Hampstead,
London UK, NW3 2QG
Received November 30, 2011; accepted December 30, 2011; Epub February 5, 2012; Published February 28, 2012
Abstract: It is estimated worldwide that over 6 million people per annum experience a burn injury. Despite advances in
management and improved survival rates, the incidence of hypertrophic scarring remains high. These scars are particularly
common after burns and are often raised, red, hard and may cause abnormal sensations. Such pathological scarring can lead
to severe functional impairment, psychological morbidity, and costly long term healthcare. Wound healing is an inherent
process which restores the integrity of the skin after injury and although scarring is a frequent by-product, the scarless wound
healing observed in early human gestational fetuses suggests that it is not an essential component of the response. This has
lead to a large body of research attempting to understand the mechanisms behind scarring and in turn prevent it. One of the
main focuses of recent research has been the role played by the growth factor TGF-β in the process of both wound healing and
scar formation. The three isoforms (TGF-β1, TGF-β2 and TGF-β3) appear to have overlapping functions and predominantly
mediate their effects through the intracellular SMAD pathway. Initial research suggested that TGF-β1 was responsible for the
fibrotic scarring response whereas the scarless wound healing seen in fetal wounds was due to increased levels of TGF-β3.
However, the reality appears to be far more complex and it is unlikely that simply altering the ratio of TGF-β isoforms will lead to
scarless wound healing. Other aspects of the TGF-β system that appear promising include the downstream mediator CTFG,
the proteoglycan decorin and the binding protein p311. Other putative mechanisms which may underlie the pathogenesis of
hypertrophic scars include excessive inflammation, excessive angiogenesis, altered levels of matrix metalloproteinases,
growth factors, and delayed apoptosis of fibrotic myofibroblasts either due to p53 genetic alterations or tensile forces across
the wound. If an effective treatment for hypertrophic scars following burns injury is to be developed then further work must be
carried out to understand the basic mechanisms of pathological scarring. (IJBT1111003)
Keywords: Burn scarring, hypertrophic scarring, pathological scarring, regeneration, TGF-β, wound healing
Address correspondence to:
Dr. K Rolfe
The Institute of Plastic Surgery Research and Education
Dept Plastic Surgery
The Royal Free Hospital
Pond St Hampstead
London, UK
NW3 2QG
Email: work@kerstinrolfe.com
Review Article
The role of the TGF-Beta family in wound healing, burns and scarring, a review
Jack W Penn, Adriaan O Grobbelaar, Kerstin J Rolfe
The Institute of Plastic Surgery, Research and Education. Dept Plastic Surgery, The Royal Free Hospital, Pond St Hampstead,
London UK, NW3 2QG
Received November 30, 2011; accepted December 30, 2011; Epub February 5, 2012; Published February 28, 2012
Abstract: It is estimated worldwide that over 6 million people per annum experience a burn injury. Despite advances in
management and improved survival rates, the incidence of hypertrophic scarring remains high. These scars are particularly
common after burns and are often raised, red, hard and may cause abnormal sensations. Such pathological scarring can lead
to severe functional impairment, psychological morbidity, and costly long term healthcare. Wound healing is an inherent
process which restores the integrity of the skin after injury and although scarring is a frequent by-product, the scarless wound
healing observed in early human gestational fetuses suggests that it is not an essential component of the response. This has
lead to a large body of research attempting to understand the mechanisms behind scarring and in turn prevent it. One of the
main focuses of recent research has been the role played by the growth factor TGF-β in the process of both wound healing and
scar formation. The three isoforms (TGF-β1, TGF-β2 and TGF-β3) appear to have overlapping functions and predominantly
mediate their effects through the intracellular SMAD pathway. Initial research suggested that TGF-β1 was responsible for the
fibrotic scarring response whereas the scarless wound healing seen in fetal wounds was due to increased levels of TGF-β3.
However, the reality appears to be far more complex and it is unlikely that simply altering the ratio of TGF-β isoforms will lead to
scarless wound healing. Other aspects of the TGF-β system that appear promising include the downstream mediator CTFG,
the proteoglycan decorin and the binding protein p311. Other putative mechanisms which may underlie the pathogenesis of
hypertrophic scars include excessive inflammation, excessive angiogenesis, altered levels of matrix metalloproteinases,
growth factors, and delayed apoptosis of fibrotic myofibroblasts either due to p53 genetic alterations or tensile forces across
the wound. If an effective treatment for hypertrophic scars following burns injury is to be developed then further work must be
carried out to understand the basic mechanisms of pathological scarring. (IJBT1111003)
Keywords: Burn scarring, hypertrophic scarring, pathological scarring, regeneration, TGF-β, wound healing
Address correspondence to:
Dr. K Rolfe
The Institute of Plastic Surgery Research and Education
Dept Plastic Surgery
The Royal Free Hospital
Pond St Hampstead
London, UK
NW3 2QG
Email: work@kerstinrolfe.com
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