Salomon G D, Kasid A, Bernstein E, Buresh C, Director E, Norton J A
Surgery Branch, National Cancer Institute/NIH, Bethesda, MD 20892.
Surgery. 1990 Aug;108(2):318-22; discussion 322-3.
The function of transforming growth factor-beta (TGF-beta) in vivo remains unknown despite the fact that it has been identified in numerous biologic processes involving the regulation of cell growth including tissue repair. Doxorubicin is a potent antitumor drug that has been shown to have detrimental effects on wound healing. With specific complementary DNA probes for TFG-beta and type 1 collagen, RNA from wounds of rats treated with saline solution and doxorubicin was analyzed for the expression of each gene at different times after wounding. In a second study, either 2 micrograms exogenous TGF-beta or vehicle was added to wounds of rats treated with doxorubicin, and wound RNA was analyzed in a similar manner. In wounds from rats treated with saline solution, messenger RNA (mRNA) for TGF-beta peaks on day 7 after wounding and is also elevated on days 3 and 10; mRNA for collagen is elevated on days 7 and 10. Doxorubicin decreases mRNA for TGF-beta and collagen on each day. Topical application of TGF-beta to wounds of rats treated with doxorubicin increases collagen mRNA levels to normal or supranormal levels. This study suggests that the impaired healing induced by doxorubicin may be a result of decreased gene expression for TGF-beta and that topical replacement of this growth factor may correct the defect.
尽管转化生长因子-β（TGF-β）已在包括组织修复在内的众多涉及细胞生长调节的生物过程中被发现，但其在体内的功能仍不清楚。阿霉素是一种有效的抗肿瘤药物，已被证明对伤口愈合有不利影响。使用针对TFG-β和I型胶原的特异性互补DNA探针，分析用盐溶液和阿霉素处理的大鼠伤口在受伤后不同时间的RNA，以检测每个基因的表达。在第二项研究中，将2微克外源性TGF-β或赋形剂添加到用阿霉素处理的大鼠伤口中，并以类似方式分析伤口RNA。在用盐溶液处理的大鼠伤口中，TGF-β的信使核糖核酸（mRNA）在受伤后第7天达到峰值，在第3天和第10天也升高；胶原的mRNA在第7天和第10天升高。阿霉素使每天的TGF-β和胶原mRNA降低。将TGF-β局部应用于用阿霉素处理的大鼠伤口，可使胶原mRNA水平升高至正常或超正常水平。这项研究表明，阿霉素诱导的愈合受损可能是TGF-β基因表达降低的结果，局部补充这种生长因子可能纠正这一缺陷。
