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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Transforming growth factor beta 1 dependent regulation of Tenascin-C in radiation impaired wound healing.
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Transforming growth factor beta 1 dependent regulation of Tenascin-C in radiation impaired wound healing.

机译：Tenascin-C的转化生长因子β1依赖性调节在放射损伤伤口愈合中的作用。

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BACKGROUND: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region fibrocontractive wound healing disorders occur. Tenascin-C is significantly increased in fibrotic tissue conditions and can be stimulated by the transcription factor NFkappaB p65. Previous studies showed a reduction of irradiation induced fibrosis during the wound healing process by anti-TGFbeta(1)-treatment. The aim of the study was to clarify the question whether Tenascin-C expression is elevated in radiation impaired wounds and whether anti-TGFbeta(1)-treatment is capable to influence Tenascin-C and NFkappaB expression. MATERIAL AND METHODS: Wistar rats (male, weight 300-500g) underwent preoperative irradiation of the head and neck region with 40Gy, fractionated four times 10Gy (16 animals), whereas 8 non-irradated animals served as a control. Four weeks after irradiation a free myocutaneous gracilis flap taken from the groin was transplanted to the neck. Eightanimals additionally received 5microg anti-TGFbeta(1) into the graft bed by intradermal injection prior to each fraction of irradiation and on days 1-7 post-operation. On day 14 and 28 following surgery immunohistochemistry (ABC-POX method) was performed assessing the cytoplasmic NFkappaB and Tenascin-C staining in the transition area between transplant and graft bed. For quantitative considerations the labeling index (ratio: positive cells/total cells) was determined. RESULTS: A significantly altered expression of Tenascin-C in the preirradiated tissue was observed following anti-TGFbeta(1)-treatment. NFkappaB protein was upregulated in irradiated animals and was significantly reduced in the anti-TGFbeta(1) treated group on day 28 after transplantation. CONCLUSIONS: Tenascin-C expression is prolonged in irradiated animals as compared to non-irradiated tissue. Tenascin-C seems to be regulated by TGFbeta(1) as the application of TGFbeta(1)-neutralizing antibodies reduces Tenascin-C expression. Tenascin-C is a potentially useful marker for tissue remodeling due to its restricted distribution in adult and healthy tissue and a hallmark for developing fibrosis.
机译：背景：在头颈部鳞状上皮细胞癌的消融手术前，术前放疗后发生了纤维收缩性伤口愈合障碍。腱生蛋白-C在纤维化组织条件下显着增加，并且可以被转录因子NFkappaB p65刺激。先前的研究表明，通过抗TGFbeta（1）-治疗减少了伤口愈合过程中辐射诱发的纤维化。该研究的目的是阐明在辐射受损的伤口中腱糖蛋白-C表达是否升高以及抗TGFbeta（1）-治疗是否能够影响腱糖蛋白-C和NFkappB表达的问题。材料与方法：Wistar大鼠（雄性，体重300-500g）接受40Gy术前照射头颈部区域，分为10Gy的四倍（16只动物），而8只未受辐照的动物作为对照。照射后四周，将取自腹股沟的游离肌腱肌皮瓣移植到颈部。在辐照的每个阶段之前和术后1-7天，八头动物还通过皮内注射将5microg抗TGFbeta（1）接受了皮下注射。在手术后第14和28天，进行免疫组织化学（ABC-POX法），评估移植物和移植床之间过渡区域的细胞质NFkappaB和腱生蛋白-C染色。出于定量考虑，确定了标记指数（比率：阳性细胞/总细胞）。结果：在抗TGFbeta（1）处理后，预照射的组织中的Tenascin-C表达明显改变。 NFkappaB蛋白在受辐照的动物中上调，并且在移植后第28天在抗TGFbeta（1）处理组中显着降低。结论：与非辐照组织相比，辐照动物中的腱生蛋白-C表达延长。 Tenascin-C似乎受到TGFbeta（1）的调节，因为TGFbeta（1）中和抗体的应用降低了Tenascin-C的表达。腱生蛋白-C由于其在成人和健康组织中的分布受限以及发展为纤维化的标志，因此是组织重塑的潜在有用标记。

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