INFLUENCE OF THE EXTRACELLULAR-MATRIX ON THE PROLIFERATIVE RESPONSE OF HUMAN-SKIN FIBROBLASTS TO SERUM AND PURIFIED PLATELET-DERIVED GROWTH-FACTOR

INFLUENCE OF THE EXTRACELLULAR-MATRIX ON THE PROLIFERATIVE RESPONSE OF HUMAN-SKIN FIBROBLASTS TO SERUM AND PURIFIED PLATELET-DERIVED GROWTH-FACTOR
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DOI:
10.1002/jcp.1041370123
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发表时间:
1988-10-01
影响因子:
5.6
通讯作者:
MCPHERSON, JM
MCPHERSON, JM
中科院分区:
生物学2区
文献类型:
--
作者:
RHUDY, RW;MCPHERSON, JM

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用重组牛I型胶原凝胶培养成人皮肤成纤维细胞,其浓度范围为2.5-35.0 mg/ml,用~3H-胸腺嘧啶核苷掺入法测定,其增殖率下降40%-60%。当细胞在人和牛血清中培养时,这种抑制作用明显。将凝胶干燥成薄膜可以消除纤维状胶原对细胞增殖的抑制作用。细胞贴壁研究表明,不同底物上细胞增殖率的差异不仅仅是由于初始贴壁的不同。对纯化的血小板衍生生长因子(PDGF)的研究表明,与塑料相比,细胞在胶原凝胶上培养时对该因子的反应性降低,这在很大程度上导致了在有血清存在的情况下细胞的增殖活性降低。总DNA测定证实,在胶原凝胶上培养的成纤维细胞在PDGF刺激下的增殖活性降低。结果表明,细胞对PDGF的反应性降低不仅仅是因为因子结合到纤维状胶原凝胶上或细胞无法接触到。这些数据表明,在胶原凝胶上培养的成纤维细胞增殖率下降是细胞外基质影响细胞对可溶性有丝分裂介质反应能力的直接结果。
The culture of adult human skin fibroblasts on reconstituted bovine type I fibrillar collagen gels, ranging in concentration from 2.5-35.0 mg/ml, results in a reduction in proliferation rate by 40%-60% as measured by (3H) thymidine incorporation. The suppressive effect was noted when cells were cultured in both human and bovine serum. Drying the gels into thin films abolishes the suppressive effect of the fibrillar collagen on cell proliferation. Cell attachment studies showed that differences in the proliferation rate of cells on the various substrata were not simply due to differences in initial attachment. Studies with purified platelet-derived growth factor (PDGF) demonstrated that the reduced responsiveness of cells to this factor, when cultured on collagen gels as compared to plastic, was largely responsible for the reduced proliferative activity of the cells when cultured in the presence of serum. The reduced proliferative activity of fibroblasts in response to PDGF, when cultured on collagen gels, was confirmed by total DNA determination. It was shown that the reduced responsiveness of cells to PDGF was not simply because the factor bound to the fibrillar collagen gel or was inaccessible to the cells. The data indicate that the reduced proliferation rate of fibroblasts cultured on collagen gels is a direct result of the influence of the extracellular matrix on the cells'' ability to respond to a soluble mitogenic mediator.