Kipp D, Wilson S, Gosiewska A, Peterkofsky B
Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20892, USA.
Wound Repair Regen. 1995 Apr-Jun;3(2):192-203. doi: 10.1046/j.1524-475X.1995.30211.x.
Poor wound healing during vitamin C deficiency is thought to be due to decreased hydroxylation of proline residues in collagen. In non-repair connective tissues of guinea pigs, however, procollagen gene expression is not decreased until weight loss occurs during the third and fourth weeks of scurvy (phase II) with only a moderate decrease in proline hydroxylation. Decreased procollagen gene expression is related to the induction of insulin-like growth factor binding proteins 1 and 2 that inhibit insulin-like growth factor-I action. We examined wound healing and granulation tissue formation during phase I of vitamin C deficiency. Synthetic sponges were implanted on day 7 of vitamin C deficiency and analyzed at 6 and 10 days after surgery, when there was no weight loss or induction of insulin-like growth factor binding proteins. Healing of incisions was almost complete at 10 days after surgery in normal controls but not in scorbutic animals. The area around the incision and implant exhibited excessive angiogenesis and hemorrhaging of vessels in the scorbutic animals at 6 and 10 days after surgery. At 10 days after surgery, collagen synthesis in the implants of scorbutic guinea pigs was 36% lower than control values, with a normal extent of proline hydroxylation. Concentrations of messenger RNAs for types I and III procollagens were slightly increased by scurvy at 6 days after surgery but were decreased by 26% and 40%, respectively, at 10 days. Fibronectin mRNA levels were unaffected by scurvy at both time points. Our results suggest that poor wound healing in phase I of scurvy may be related to defective interstitial procollagen gene expression and defective blood vessel formation, but it does not involve inhibition of proline hydroxylation or induction of insulin-like growth factor binding proteins. mRNA for insulin-like growth factor-II, transforming growth factor-beta(1), and transforming growth factor-beta(2) were significantly expressed in implants, but their patterns of expression did not correlate with changes in procollagen gene expression.
维生素C缺乏时伤口愈合不良被认为是由于胶原蛋白中脯氨酸残基的羟基化减少所致。然而，在豚鼠的非修复性结缔组织中，直到坏血病第三和第四周体重减轻时（II期），前胶原基因表达才会下降，此时脯氨酸羟基化仅有中度降低。前胶原基因表达下降与胰岛素样生长因子结合蛋白1和2的诱导有关，它们会抑制胰岛素样生长因子-I的作用。我们研究了维生素C缺乏I期的伤口愈合和肉芽组织形成。在维生素C缺乏第7天植入合成海绵，并在术后6天和10天进行分析，此时没有体重减轻或胰岛素样生长因子结合蛋白的诱导。正常对照组术后10天时切口愈合几乎完成，但坏血病动物则不然。术后6天和10天时，坏血病动物切口和植入物周围区域出现过度血管生成和血管出血。术后10天时，坏血病豚鼠植入物中的胶原合成比对照值低36%，脯氨酸羟基化程度正常。术后6天时，坏血病使I型和III型前胶原的信使核糖核酸浓度略有增加，但在术后第10天时分别下降了26%和40%。两个时间点的纤连蛋白信使核糖核酸水平均不受坏血病影响。我们的结果表明，坏血病I期伤口愈合不良可能与间质前胶原基因表达缺陷和血管形成缺陷有关，但不涉及脯氨酸羟基化的抑制或胰岛素样生长因子结合蛋白的诱导。胰岛素样生长因子-II、转化生长因子-β(1)和转化生长因子-β(2)的信使核糖核酸在植入物中显著表达，但其表达模式与前胶原基因表达的变化无关。
