Transcription factor Egr-1 activates collagen expression in immortalized fibroblasts or fibrosarcoma cells

Transcription factor Egr-1 activates collagen expression in immortalized fibroblasts or fibrosarcoma cells
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DOI:
10.1515/bc.2002.208
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发表时间:
2002-12-01
影响因子:
3.7
通讯作者:
Aicher, WK
Aicher, WK
中科院分区:
生物学2区
文献类型:
--
作者:
Alexander, D;Judex, M;Aicher, WK

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Synovial fibroblasts from rheumatoid arthritis patients express elevated levels of the transcription factor Egr-1. The metabolic consequences of Egr-1 overexpression in fibroblasts are not known in detail. Therefore we searched for gene products that are differentially expressed in Egr-1(high) versus Egr-1(low) fibroblasts. Immortalized synovial fibroblasts were transfected with two different Egr-1 expression vectors. Expression of recombinant Egr-1 was confirmed by RTPCR and immunoblots. Random arbitrarily primed PCR revealed that Egr-1 induces enhanced transcription levels of the alpha1 chain of type I collagen. Increased expression of the alpha2 (I) chain could also be observed. We found enhanced levels of type I collagen propeptide in supernatants and stronger signals of alpha2 (I) protein in extracts of the Egr 1(high) expressing clone versus controls. Additionally, Egr-1 was transiently expressed in fibrosarcoma cells. These cells showed a pronounced elevation of type I collagen (alpha1) transcripts as well. Moreover, we could demonstrate that Egr-1 induces transcription of other genes including type II collagen (alpha1) and plateledderived growth factor beta1. These data suggest that upregulation of Egr-1 might contribute to fibrosis observed in rheumatoid arthritis synovium by activation of genes encoding the alpha1 and alpha2 chains of type I collagen.