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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-1high versus Egr-1low 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 α1 chain of type I collagen. Increased expression of the α2 (I) chain could also be observed. We found enhanced levels of type I collagen propeptide in supernatants and stronger signals of α2 (I) protein in extracts of the Egr 1high expressing clone versus controls. Additionally, Egr-1 was transiently expressed in fibrosarcoma cells. These cells showed a pronounced elevation of type I collagen (α1) transcripts as well. Moreover, we could demonstrate that Egr-1 induces transcription of other genes including type II collagen (α1) and plateledderived growth factor β1. These data suggest that upregulation of Egr-1 might contribute to fibrosis observed in rheumatoid arthritis synovium by activation of genes encoding the α1 and α2 chains of type I collagen.

Transcription Factor Egr-1 Activates Collagen Expression in Immortalized Fibroblasts or Fibrosarcoma Cells