Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells.
Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells.
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DOI：
10.1006/exer.1994.1152
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发表时间：
1994-12
影响因子：
3.4
通讯作者：
Steven E. Wilson;Yu-Guang He;Jian Weng;James D. Zieske;James V. Jester;Gregory S. Schultz
中科院分区：
文献类型：
--
作者：
Steven E. Wilson;Yu-Guang He;Jian Weng;James D. Zieske;James V. Jester;Gregory S. Schultz
我们试图确定外源性表皮生长因子（EGF），肝素结合EGF（HB-EGF），转化生长因子α（TGF-α）在无血清化学成分确定的培养基中，研究了TGF-α、单链前体肝细胞生长因子（SC-HGF）、双链成熟HGF（DC-HGF）和角质形成细胞生长因子（KGF）对人角膜上皮细胞第一代培养物增殖、运动和分化的影响。EGF、HB-EGF、TGF-α、SC-HGF、DC-HGF、KGF或生长因子的组合对增殖的作用通过计数培养3周后存在的细胞和通过细胞周期特异性核增殖抗原Ki-67的免疫染色来测量。上皮细胞运动的因素的影响进行了评估的细胞迁移从汇合的细胞岛的照片的形态学分析。生长因子对上皮细胞分化的影响通过对上皮细胞岛进行角蛋白K3的免疫染色和通过对角蛋白K3的Western印迹来确定。EGF，单独或与KGF和SC-HGF组合，显着刺激运动的上皮细胞在细胞融合岛的周边，并诱导细长的细胞形态。TGF-α、HB-EGF和DC-HGF产生类似于EGF的运动效应。迁移细胞对EGF、HB-EGF、TGF-α或DC-HGF的增殖反应减弱，而汇合岛中心的非迁移上皮细胞对生长因子的反应继续增殖。EGF、HB-EGF、TGF α或DC-HGF抑制了岛边缘和中心上皮细胞中分化相关标记物角蛋白K3的表达。KGF刺激角膜上皮细胞增殖，在低密度和融合的细胞岛。KGF不影响角蛋白K3的表达和上皮细胞的迁移。SC-HGF对角膜上皮细胞无影响。这些结果表明EGF、HB-EGF、TGF-α和DC-HGF对角膜上皮细胞增殖、运动和分化的作用不同于KGF和SC-HGF。EGF、HB-EGF、TGF-α和DC-HGF诱导以低细胞密度铺板的细胞或位于汇合岛边缘的细胞中上皮细胞形态和运动性的变化。因此，这些效应似乎取决于细胞-细胞接触的程度。然而，EGF、HB-EGF、TGF-α或DC-HGF对角膜上皮细胞分化的抑制作用与细胞密度无关。（400字处截断摘要）
We sought to determine the effects of exogenous epidermal growth factor (EGF), heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF-alpha), single-chain precursor hepatocyte growth factor (SC-HGF), double-chain mature HGF (DC-HGF), and keratinocyte growth factor (KGF) on proliferation, motility, and differentiation of first passage cultures of human corneal epithelial cells in serum-free chemically defined medium. The effect of EGF, HB-EGF, TGF-alpha, SC-HGF, DC-HGF, KGF or combinations of the growth factors on proliferation was measured by counting cells present after 3 weeks of culture and by immunostaining for the cell-cycle-specific nuclear proliferation antigen Ki-67. The effect of the factors on epithelial cell motility was assessed by morphometric analysis of photographs of cells migrating from confluent islands of cells. The effect of growth factors on differentiation of epithelial cells were determined by immunostaining epithelial cell islands for the keratin K3 and by Western blotting for keratin K3. EGF, alone or in combination with KGF and SC-HGF, significantly stimulated motility of epithelial cells at the periphery of confluent islands of cells and induced an elongated cell morphology. TGF-alpha, HB-EGF and DC-HGF produced motility effects similar to EGF. There was diminished proliferation of the migrating cells in response to EGF, HB-EGF, TGF-alpha or DC-HGF, while non-migrating epithelial cells in the center of confluent islands continued to proliferate in response to the growth factors. EGF, HB-EGF, TGF alpha or DC-HGF inhibited expression of the differentiation-related marker keratin K3 in epithelial cells, both at the edge and at the center of the islands. KGF stimulated proliferation of corneal epithelial cells at low density and in confluent islands of cells. KGF did not affect expression of keratin K3 or migration of epithelial cells. SC-HGF had no effect on corneal epithelial cells. These results indicate that the effects of EGF, HB-EGF, TGF-alpha and DC-HGF on corneal epithelial cell proliferation, motility and differentiation vary from those of KGF and SC-HGF. EGF, HB-EGF, TGF-alpha and DC-HGF induced changes in epithelial cell morphology and motility in cells plated at low cell density or in cells located at the edge of a confluent island. Thus, these effects appear to be dependent on the extent of cell-cell contact. The inhibitory effect of EGF, HB-EGF, TGF-alpha or DC-HGF on corneal epithelial cell differentiation, however, is independent of cell density.(ABSTRACT TRUNCATED AT 400 WORDS)