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

Alexander, Dorothea and Judex, Martin and Meyringer, Rotraud and Weis-Klemm, Michaela and Gay, Steffen and Mueller-Ladner, Ulf and Aicher, Wilhelm K. (2002) Transcription factor Egr-1 activates collagen expression in immortalized fibroblasts or fibrosarcoma cells. BIOLOGICAL CHEMISTRY, 383 (12). pp. 1845-1853. ISSN 1431-6730

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: RHEUMATOID-ARTHRITIS; SYNOVIAL FIBROBLASTS; GENE-EXPRESSION; B-CELLS; GROWTH; PROMOTER; MICE; PROLIFERATION; CARTILAGE; DIFFERENTIATION; gene regulation; rheumatoid arthritis; synovial fibroblasts; transcription factors
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Aug 2021 11:01
Last Modified: 26 Aug 2021 11:01
URI: https://pred.uni-regensburg.de/id/eprint/39587

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