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首页> 外文OA文献 >Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.
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Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

机译：在用重组PDGF-BB治疗的积极愈合的人类伤口中检测血小板衍生的生长因子（PDGF）-AA，在慢性不愈合伤口中不存在PDGF。

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Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-beta receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB.
机译：用重组血小板衍生生长因子-BB（rPDGF-BB）治疗的某些人类慢性皮肤伤口显示出增加的愈合以及成纤维细胞的活化和肉芽组织的形成。为了确定内源性PDGF是否与愈合和未愈合的皮肤溃疡表型相关，我们开发了能够识别PDGF，AA，AB和BB二聚体的三种同工型，并能够区分两个交替剪接的A链转录本的单克隆抗体。我们在正常皮肤和未愈合的皮肤溃疡中检测到很少的PDGF亚型表达。相反，在用rPDGF-BB治疗的外科创面的急性伤口和慢性溃疡中，发现PDGF-AA（长型）的水平明显升高。在两种类型的伤口中，主要在毛细血管和成纤维细胞中都检测到PDGF-AA升高，尽管在用rPDGF-BB治疗的慢性伤口中，PDGF-AA的广泛表达有所延迟。通过持续治疗，可以优先结合细胞外基质的长形PDGF-AA仅在毛细血管中表达，而成纤维细胞开始合成短形PDGF-AA。在毛细血管内，所有内皮细胞以及数量不等的周细胞和平滑肌细胞均含有PDGF-AA。在所有伤口中，巨噬细胞和角质形成细胞不是主要的贡献者。虽然PDGF-BB和PDGF-AB存在于少数愈合伤口中，但它们的含量通常低于PDGF-AA。在正常皮肤和肉芽组织中发现仅结合PDGF-BB而不结合其他同工型的PDGF-β受体，为用外源性rPDGF-BB治疗人类慢性伤口提供了分子基础。

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