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2013 ; 2
(5
): 225-237
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Transforming Growth Factor Beta Signaling in Cutaneous Wound Healing: Lessons
Learned from Animal Studies
#MMPMID24761336
Finnson KW
; Arany PR
; Philip A
Adv Wound Care (New Rochelle)
2013[Jun]; 2
(5
): 225-237
PMID24761336
show ga
SIGNIFICANCE: Wound healing is a complex physiological process involving a
multitude of growth factors, among which transforming growth factor beta (TGF-?)
has the broadest spectrum of effects. Animal studies have provided key
information on the mechanisms of TGF-? action in wound healing and have guided
the development of therapeutic strategies targeting the TGF-? pathway to improve
wound healing and scarring outcome. RECENT ADVANCES: Development of
tissue-specific expression systems for overexpression or knockout of TGF-?
signaling pathway components has led to novel insight into the role of TGF-?
signaling in wound healing. This work has also identified molecules that might
serve as molecular targets for the treatment of pathological skin conditions such
as chronic wounds and excessive scarring (fibrosis). CRITICAL ISSUES: Many of the
mouse models with genetic alterations in the TGF-? signaling pathway develop an
underlying skin abnormality, which may pose some limitations on the
interpretation of wound-healing results obtained in these animals. Also, TGF-?'s
pleiotropic effects on many cell types throughout all phases of wound healing
present a challenge in designing specific strategies for targeting the TGF-?
signaling pathway to promote wound healing or reduce scarring. FUTURE DIRECTIONS:
Further characterization of TGF-? signaling pathway components using inducible
tissue-specific overexpression or knockout technology will be needed to
corroborate results obtained in mouse models that display a skin phenotype, and
to better understand the role of TGF-? signaling during distinct phases of the
wound-healing process. Such studies will also provide a better understanding of
how TGF-? mediates its autocrine, paracrine, and double paracrine effects on
cellular responses in vivo during wound healing.
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