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Expression and possible mechanism of c-ski, a novel tissue repair-related gene during normal and radiation-impaired wound healing

ABSTRACT C‐ski is a complicated regulating factor for fibroblast proliferation and an important co‐repressor of Smad3. Although inhibiting Smad3 activity can markedly promote wound healing because Smad3 mediates the role of transforming growth factor‐β in inhibiting cell proliferation and inducing c...

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Published in:Wound repair and regeneration 2006-03, Vol.14 (2), p.162-171
Main Authors: Liu, Xia, Zhang, En, Li, Ping, Liu, Jianzhong, Zhou, Ping, Gu, Da-yong, Chen, Xingyun, Cheng, Tianmin, Zhou, Yuanguo
Format: Article
Language:English
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Summary:ABSTRACT C‐ski is a complicated regulating factor for fibroblast proliferation and an important co‐repressor of Smad3. Although inhibiting Smad3 activity can markedly promote wound healing because Smad3 mediates the role of transforming growth factor‐β in inhibiting cell proliferation and inducing cell apoptosis; there has been no report on whether c‐ski is expressed during wound healing and the relationship between its expression and wound healing. By establishing animal models of normal and radiation‐impaired wound healing and using immunohistochemistry, in situ hybridization, and reverse transcription‐polymerase chain reaction, we found that c‐ski was expressed after wounding and reached its peak on day 9 and then significantly decreased. C‐ski was present in all repair cells, and was especially prominent in fibroblasts. Compared with the control side, the irradiated side showed a lower expression of c‐ski on postwound days 3–9, but higher on day 15, and not significantly different after the wound was healed. The expression of Smad3 was in contrast to the c‐ski and cellular proliferation was similar to that of c‐ski expression. The apoptosis index was significantly higher on the irradiated side on days 3–9 compared with the control side. In vitro, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide results showed that c‐ski could reverse the inhibitory role of Smad3 on fibroblast proliferation. Flow cytometry analysis found that c‐ski also diminished fibroblast apoptosis induced by Smad3 transfection. These results suggest that there is not only obvious expression of this regulatory protein but there is also a significant change in the levels of c‐ski during wound healing. Its in vivo expression pattern and experiments in vitro suggest that c‐ski may be involved in tissue repair by repressing Smad3 activity. Radiation can reduce c‐ski and increase Smad3 expression, resulting in elevated Smad3 activity, resulting in diminished cell proliferation, cell apoptosis, and wound‐healing delays.
ISSN:1067-1927
1524-475X
DOI:10.1111/j.1743-6109.2006.00106.x