Flanders KC, Major CD, Arabshahi A, Aburime EE, Okada MH, Fujii M, Blalock TD, Schultz GS, Sowers A, Anzano MA, Mitchell JB, Russo A, Roberts AB, et al.
The American journal of pathology. Date of publication 2003 Dec 1;volume 163(6):2247-57.
1. Am J Pathol. 2003 Dec;163(6):2247-57.
Interference with transforming growth factor-beta/ Smad3 signaling results in
accelerated healing of wounds in previously irradiated skin.
Flanders KC(1), Major CD, Arabshahi A, Aburime EE, Okada MH, Fujii M, Blalock TD,
Schultz GS, Sowers A, Anzano MA, Mitchell JB, Russo A, Roberts AB.
Author information:
(1)Laboratory of Cell Regulation and Carcinogenesis and the Radiation Oncology
Branch, National Cancer Institute, National Institutes of Health, Bethesda,
Maryland 21201, USA.
Transforming growth factor (TGF)-beta regulates many aspects of wound repair
including inflammation, chemotaxis, and deposition of extracellular matrix. We
previously showed that epithelialization of incisional wounds is accelerated in
mice null for Smad3, a key cytoplasmic mediator of TGF-beta signaling. Here, we
investigated the effects of loss of Smad3 on healing of wounds in skin previously
exposed to ionizing radiation, in which scarring fibrosis complicates healing.
Cutaneous wounds made in Smad3-null mice 6 weeks after irradiation showed
decreased wound widths, enhanced epithelialization, and reduced numbers of
neutrophils and myofibroblasts compared to wounds in irradiated wild-type
littermates. Differences in breaking strength of wild-type and Smad3-null wounds
were not significant. As shown previously for neutrophils, chemotaxis of primary
dermal fibroblasts to TGF-beta required Smad3, but differentiation of fibroblasts
to myofibroblasts by TGF-beta was independent of Smad3. Previous
irradiation-enhanced induction of connective tissue growth factor mRNA in
wild-type, but not Smad3-null fibroblasts, suggested that this may contribute to
the heightened scarring in irradiated wild-type skin as demonstrated by
Picrosirius red staining. Overall, the data suggest that attenuation of Smad3
signaling might improve the healing of wounds in previously irradiated skin
commensurate with an inhibition of fibrosis.
PMCID: PMC1892357
PMID: 14633599 [Indexed for MEDLINE]
