Pierce G F, Tarpley J E, Yanagihara D, Mustoe T A, Fox G M, Thomason A
Department of Experimental Pathology, Amgen Inc., Thousand Oaks, California 91320.
Am J Pathol. 1992 Jun;140(6):1375-88.
Recombinant platelet-derived growth factor (BB homodimer, rPDGF-BB), transforming growth factor beta 1 (rTGF-beta 1), and basic fibroblast growth factor (rbFGF) can accelerate healing of soft tissues. However, little information is available characterizing the components of wound matrix induced by these growth factors and the molecular mechanisms underlying accelerated repair and wound maturation. In this study, the composition, quantity, and rate of extracellular matrix deposition within growth factor-treated lapine ear excisional wounds were analyzed at different stages of healing using specific histochemical and immunohistochemical stains, coupled with image analysis techniques. Single application of optimal concentrations of each growth factor accelerated normal healing by 30% (P less than 0.0003); rPDGF-BB markedly augmented early glycosaminoglycan (GAG) and fibronectin deposition, but induced significantly greater levels of collagen later in the repair process, compared with untreated wounds rTGF-beta 1 treatment led to rapidly enhanced collagen synthesis and maturation, without increased GAG deposition. In contrast, rbFGF treatment induced a predominantly angiogenic response in wounds, with a marked increase in endothelia and neovessels (P less than 0.0001), and increased wound collagenolytic activity (P less than 0.03). rbFGF-treated wounds did not evolve into collagen-containing scars and continued to accumulate only provisional matrix well past wound closure. These results provide new evidence that growth factors influence wound repair via different mechanisms: 1) rPDGF-BB accelerates deposition of provisional wound matrix; 2) rTGF-beta 1 accelerates deposition and maturation of collagen; and 3) rbFGF induces a profound monocellular angiogenic response which may lead to a marked delay in wound maturation, and the possible loss of the normal signal(s) required to stop repair. These results suggest that specific growth factors may selectively regulate components of the repair response by differing mechanisms, offering the potential for targeted therapeutic intervention.
重组血小板衍生生长因子（BB 同二聚体，rPDGF - BB）、转化生长因子β1（rTGF -β1）和碱性成纤维细胞生长因子（rbFGF）可加速软组织愈合。然而，关于这些生长因子诱导的伤口基质成分以及加速修复和伤口成熟的分子机制的信息却很少。在本研究中，使用特定的组织化学和免疫组织化学染色结合图像分析技术，分析了生长因子处理的兔耳切除伤口在愈合不同阶段细胞外基质沉积的组成、数量和速率。单独应用每种生长因子的最佳浓度可使正常愈合加速 30%（P 小于 0.0003）；与未处理的伤口相比，rPDGF - BB 显著增加了早期糖胺聚糖（GAG）和纤连蛋白的沉积，但在修复过程后期诱导了更高水平的胶原蛋白。rTGF -β1 处理导致胶原蛋白合成和成熟迅速增强，而 GAG 沉积没有增加。相比之下，rbFGF 处理在伤口中主要诱导血管生成反应，内皮细胞和新血管显著增加（P 小于 0.0001），并且伤口胶原酶活性增加（P 小于 0.03）。经 rbFGF 处理的伤口不会演变成含胶原蛋白的瘢痕，并且在伤口闭合后很长时间内仅继续积累临时基质。这些结果提供了新的证据，表明生长因子通过不同机制影响伤口修复：1）rPDGF - BB 加速临时伤口基质的沉积；2）rTGF -β1 加速胶原蛋白的沉积和成熟；3）rbFGF 诱导深刻的单细胞血管生成反应，这可能导致伤口成熟明显延迟，以及可能丧失停止修复所需的正常信号。这些结果表明，特定的生长因子可能通过不同机制选择性调节修复反应的成分，为靶向治疗干预提供了潜力。
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