APPEARANCE OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR IN WOUND FLUID AS A RESPONSE TO INJURY
APPEARANCE OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR IN WOUND FLUID AS A RESPONSE TO INJURY
复制标题
DOI：
10.1073/pnas.90.9.3889
复制
发表时间：
1993-05-01
影响因子：
11.1
通讯作者：
KLAGSBRUN, M
中科院分区：
文献类型：
--
作者：
MARIKOVSKY, M;BREUING, K;KLAGSBRUN, M
从猪部分皮层切除伤口中获取伤口液并分析肝素结合生长因子。检测到两种肝素结合生长因子活性，一种相对较小的活性是用 0.65 M 氯化钠从肝素亲和柱洗脱的，一种主要活性是用 1.1 M 氯化钠洗脱的。这些活性在受伤后 1 小时伤口液中不存在，但在受伤后 1 天出现，在受伤后 2-3 天达到最大，并且在受伤后 8 天检测不到。通过使用特异性抗 PDGF 中和抗体，将用 0.65 M NaCl 洗脱的肝素结合生长因子鉴定为血小板衍生生长因子 (PDGF) 样活性。通过多种标准，用 1.1 M 氯化钠洗脱的肝素结合生长因子在结构上与肝素结合表皮生长因子 (EGF) 样生长因子 (HB-EGF) 相关，包括与肝素亲和柱结合并用 1.1 M 氯化钠洗脱、与 I-125-EGF 与 EGF 受体的结合竞争、触发 EGF 受体的磷酸化、Western blot 上的免疫检测以及刺激成纤维细胞和角质形成细胞的生长。结论是，HB-EGF 是伤口液的主要生长因子成分，并且由于它对成纤维细胞和角质形成细胞具有促有丝分裂作用，因此它可能在伤口愈合中发挥重要作用。
Wound fluid was obtained from porcine partial-thickness excisional wounds and analyzed for heparin-binding growth factors. Two heparin-binding growth factor activities were detected, a relatively minor one that was eluted from a heparin affinity column with 0.65 M NaCl and a major one that was eluted with 1.1 M NaCl. These activities were not present in wound fluid 1 hr after injury but appeared 1 day after injury, were maximal 2-3 days after injury, and were not detectable by 8 days after injury. The heparin-binding growth factor eluted with 0.65 M NaCl was identified as a platelet-derived growth factor (PDGF)-like activity by the use of specific anti-PDGF neutralizing antibodies. The heparin-binding growth factor eluted with 1.1 M NaCl was shown to be structurally related to heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) by several criteria, including binding to heparin affinity columns and elution with 1.1 M NaCl, competition with the binding of I-125-EGF to the EGF receptor, triggering phosphorylation of the EGF receptor, immunodetection on a Western blot, and stimulation of fibroblast and keratinocyte growth. It was concluded that HB-EGF is a major growth factor component of wound fluid and, since it is mitogenic for fibroblasts and keratinocytes, that it might play an important role in wound healing.