Randall K, Coggle J E
Department of Radiation Biology, St Bartholomews Medical College, Charterhouse Square, London, UK.
Int J Radiat Biol. 1995 Sep;68(3):301-9. doi: 10.1080/09553009514551231.
Transforming growth factor-beta (TGF beta 1) plays a central role in wound healing, so its perturbation by radiation may contribute to the acute and late effects seen in irradiated skin. TGF beta 1 mRNA expression was measured by PCR, in the skin of the CD1 and CBA mouse, exposed to Sr-90 beta from an 11-mm diameter source. TGF beta 1 mRNA expression increased sharply after doses between 1 and 10 Gy and plateaued at approximately 200% above controls after doses between 20 and 50 Gy. Immunohistochemistry showed that the TGF beta 1 protein was confined to the dermis and suprabasal cells with none in basal cells. A dose of 50 Gy produces an acute desquamative reaction in 100% of mice that is resolved in 30 days. After the same dose, TGF beta 1 mRNA expression fell below the controls at 3 h (-9.4% in the CD1 and -44% in the CBA mouse); rose sharply at 6-12 h (+124% CD1, +230% CBA), returned to control levels by 24-48 h, then rose progressively to approximately 200% above the controls between days 7 and 14. TGF beta 1 mRNA expression remained elevated at 100-200% above controls until the end of the experiment at 55 days. The significance of these changes in TGF beta 1 is discussed in the context of the early stress response reaction to radiation, the acute inflammatory and the later chronic fibrosis of the skin.
转化生长因子-β(TGF-β1)在伤口愈合中起核心作用,因此其受辐射干扰可能导致辐照皮肤出现急性和晚期效应。通过PCR检测了暴露于直径11毫米源的Sr-90β射线的CD1和CBA小鼠皮肤中TGF-β1 mRNA的表达。在1至10 Gy剂量后,TGF-β1 mRNA表达急剧增加,在20至50 Gy剂量后,其表达稳定在比对照高约200%的水平。免疫组织化学显示,TGF-β1蛋白局限于真皮和基底上层细胞,基底细胞中无表达。50 Gy的剂量会使100%的小鼠产生急性脱屑反应,该反应在30天内消退。相同剂量照射后,TGF-β1 mRNA表达在3小时时低于对照水平(CD1小鼠中降低了9.4%,CBA小鼠中降低了44%);在6至12小时时急剧上升(CD1小鼠中上升了124%,CBA小鼠中上升了230%),在24至48小时时恢复到对照水平,然后在第7天至14天之间逐渐上升至比对照高约200%。直到实验第55天结束,TGF-β1 mRNA表达一直维持在比对照高100 - 200%的水平。本文在辐射早期应激反应、皮肤急性炎症和后期慢性纤维化的背景下讨论了TGF-β1这些变化的意义。