PURIFICATION AND CHARACTERIZATION OF A NEWLY IDENTIFIED GROWTH-FACTOR SPECIFIC FOR EPITHELIAL-CELLS
PURIFICATION AND CHARACTERIZATION OF A NEWLY IDENTIFIED GROWTH-FACTOR SPECIFIC FOR EPITHELIAL-CELLS
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DOI：
10.1073/pnas.86.3.802
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发表时间：
1989-02-01
影响因子：
11.1
通讯作者：
AARONSON, SA
中科院分区：
文献类型：
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作者：
RUBIN, JS;OSADA, H;AARONSON, SA
在人胚肺成纤维细胞系的条件培养基中鉴定了上皮细胞特异性生长因子。该因子，暂时被称为角质形成细胞生长因子（KGF），因为它的主要活动，对这种细胞类型，纯化到均匀的组合超滤，肝素-琼脂糖亲和层析，和疏水层析C4反相HPLC柱。KGF是酸和热不稳定的，并且由一条多肽链组成。28 kDa。纯化的KGF是一种有效的上皮细胞有丝分裂原，能够刺激静止的BALB/MK表皮角质形成细胞的DNA合成> 500倍，在0.1 nM和最大nM下可检测到活性。对成纤维细胞或内皮细胞缺乏促有丝分裂活性表明KGF具有不同于任何先前表征的生长因子的靶细胞特异性。微测序揭示了一个氨基末端序列不含任何已知的蛋白质的显着同源性。人胚胎成纤维细胞释放的这种生长因子提高了KGF可能在正常上皮细胞增殖的间充质刺激中发挥作用的可能性。
A growth factor specific for epithelial cells was identified in conditioned medium of a human embryonic lung fibroblast cell line. The factor, provisionally termed keratinocyte growth factor (KGF) because of its predominant activity on this cell type, was purified to homogeneity by a combination of ultrafiltration, heparin-Sepharose affinity chromatography, and hydrophobic chromatography on a C4 reversed-phase HPLC column. KGF was both acid and heat labile and consisted of a single polypeptide chain of .apprxeq. 28 kDa. Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by > 500-fold with activity detectable at 0.1 nM and maximal nM. Lack of mitogenic activity on either fibroblasts or endothelial cells indicated that KGF possessed a target cell specificity distinct from any previously characterized growth factor. Microsequencing revealed an amino-terminal sequence containing no significant homology to any known protein. The release of this growth factor by human embryonic fibroblasts raises the possibility that KGF may play a role in mesenchymal stimulation of normal epithelial cell proliferation.