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损伤成纤维细胞单层会导致原癌基因c-fos的快速诱导。

Wounding a fibroblast monolayer results in the rapid induction of the c-fos proto-oncogene.

作者信息

Verrier B, Müller D, Bravo R, Müller R

出版信息

EMBO J. 1986 May;5(5):913-7. doi: 10.1002/j.1460-2075.1986.tb04303.x.

Abstract

The c-fos gene has previously been shown to be transiently induced within minutes after the stimulation of mouse fibroblasts with growth factors. Induction of c-fos was observed specifically with competence factors (e.g., platelet-derived growth factor), not with progression factors (e.g., platelet-poor plasma), suggesting a role for c-fos in conferring competence on fibroblasts. To test this hypothesis we have analyzed c-fos expression in NIH 3T3 cells that were made competent in a different way, namely by wounding a confluent monolayer of cells. Using antibodies raised against either a synthetic fos peptide or a beta-galactosidase--fos fusion protein, we show in this study that in the majority of cells lining the wound c-fos protein is rapidly and transiently induced to high levels. No induction is observed in cells at a distance from the wound greater than approximately 5 cell layers. Induction is equally efficient in both serum-containing and serum-free medium, and is similar in cells that were deprived of fetal calf serum for 40 h prior to making the wound. Our observations support the hypothesis that c-fos may be involved in inducing the 'competent state' in fibroblasts and suggests an early role for c-fos in wound healing and tissue regeneration.

摘要

先前的研究表明,用生长因子刺激小鼠成纤维细胞后,c-fos基因会在数分钟内被短暂诱导表达。c-fos的诱导表达是在受到感受态因子(如血小板衍生生长因子)刺激时特异性观察到的,而在促增殖因子(如乏血小板血浆)刺激时未观察到,这表明c-fos在赋予成纤维细胞感受态方面发挥作用。为了验证这一假设,我们分析了以不同方式获得感受态的NIH 3T3细胞中的c-fos表达,即通过刮伤汇合的单层细胞。在本研究中,我们使用针对合成的fos肽或β-半乳糖苷酶-fos融合蛋白产生的抗体,发现伤口边缘的大多数细胞中,c-fos蛋白迅速且短暂地被诱导至高水平。在距离伤口大于约5个细胞层的细胞中未观察到诱导现象。在含血清和无血清培养基中诱导效率相同,并且在刮伤前40小时去除胎牛血清的细胞中诱导情况相似。我们的观察结果支持了c-fos可能参与诱导成纤维细胞“感受态状态”的假设,并表明c-fos在伤口愈合和组织再生中起早期作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53bc/1166882/538ebd5be365/emboj00168-0098-a.jpg

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