| Wound healing is a natural restorative response to tissue injury, involving a complex cascade of cellular events that prepare the wound for repair, deposit new matrices and finally, mature the wound. Although many studies are focused on how to accelerate wound healing, there are still no efficient methods for hard-healing wound. Many mechanisms are involved in the regulation of healing, including inflammation reaction, growth factors, immune regulation and so on, but their differences between normal- and hard-healing varies. A common phenomenon in hard-healing wound that repair cells could not cover the wound drew our attention to seek new proliferation-promoting factor, which may aid in repair cell proliferation and then closure of wound.C-ski is cellular homolog of v-ski gene, first found in chicken. Its role in fibroblast proliferation is very complex, for example, it promotes QECs (quail embryo cells) proliferation, but inhibits MEFs (mouse embryo fibroblasts) proliferation. Skin-derived fibroblast is one of important repair cells and plays an important role during wound healing. They could modulate itself and other repair cells through self-replication, collage secretion and myofibrolbalst differentiation. Whether c-ski is expressed in skin-derived fibroblast and how it affects the function of the cell remains unclear. If it could modulate the function of skin-derived fibroblast, what's role it plays in impaired cell proliferation and impaired wound healing induced by irradiation? In the present study, we developed a rat model of wound healing and impaired wound healing induced by local soft-x ray radiation. We sought to establish the role of c-ski in wound healing by evaluating its cellular expression, time course regularity and relationship with cell proliferation, cell apoptosis and Smad3, a candidate downstream molecule of c-ski. Further cellular mechanism through which c-ski may influence fibroblast function was assessed by the analysis of four main aspects: the role of c-ski in cell proliferation, the influence on collage secretion and myofibroblast differentiation, the modulation to biphasic effect of TGF-beta on proliferation, the changes in irradiated cell and the activity of anti-apoptosis. The main results and conclusions of the study are as followed:1．Local soft-X ray radiation could delay wound healing in a dose-dependent manner from 0.5-5.21Gy. The wounds received doses in excess of 7Gy failed to heal with 40 days.2．3-9 days post-wound are the key period of wound healing due to the highest healing speed. Radiation decreased the healing speed at the key stage, which may be responsible for delayed wound healing. This decrease could be restored at latter stage, indicating radiation-induced damage could be repairable.3．Corresponding with the wound healing speed, the capacity of cell proliferation was prominent and cell apoptosis was minimal during 3-9 days, suggesting the balance of cell proliferation and apoptosis could influence wound healing. The increased apoptotic cells at days 3 and wound healed may be related respectively with inflammation disappear and tissue remodeling. Radiation-induced inactive cell proliferation and active cell apoptosis may be the key reason responsible for the delayed wound healing. 4．c-ski was detected in all three kinds of repair cells, especially rich in fibroblast. The time course regularity of c-ski expression was accordant with that of cell proliferation, indicating that c-ski maybe modulate the function of repair cells especially fibroblast, including proliferation, apoptosis, collagen secretion, myofibroblast differentiation and so on. The expression of Smad3 showed an opposite tendency to c-ski's. There were less c-ski-positive cells in irradiated granulation tissue at the key stage of healing, indicating this change may be involved in impaired wound healing. 5．c-ski could significantly promote fibroblast proliferation. Smad3 markedly inhibit proliferation, while Smad2 had no effect on proliferation. C-ski also could lessen th... |
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