ArticleThe Journal of clinical investigation1993
Mithramycin selectively inhibits collagen-alpha 1(I) gene expression in human fibroblast.
Article in The Journal of clinical investigation, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 49 citations in OpenAlex.
- Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis.Journal of biomedical research · 2014Review
- Molecular insight into substrate recognition and catalysis of Baeyer-Villiger monooxygenase MtmOIV, the key frame-modifying enzyme in the biosynthesis of anticancer agent mithramycin.ACS chemical biology · 2013Article
- Myocardin-related transcription factor-A complexes activate type I collagen expression in lung fibroblasts.The Journal of biological chemistry · 2011Article
- Epigenetic modulation of the protein kinase A RIIα (PRKAR2A) gene by histone deacetylases 1 and 2 in human smooth muscle cells.Journal of cellular and molecular medicine · 2011Article
- A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression.Molecular biology of the cell · 2009Article
- Ring-Sp1 decoy oligonucleotide effectively suppresses extracellular matrix gene expression and fibrosis of rat kidney induced by unilateral ureteral obstruction.Gene therapy · 2006Article
- Regulation of histone deacetylase 4 expression by the SP family of transcription factors.Molecular biology of the cell · 2006Article
- Inhibition of collagen gene expression in systemic sclerosis dermal fibroblasts by mithramycin.Annals of the rheumatic diseases · 2005Article
- The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis.The American journal of pathology · 2005Article
- Article
- Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1-independent mechanism.Molecular biology of the cell · 2004Article
- Alterations in the regulation of expression of the alpha 1(I) collagen gene (COL1A1) in systemic sclerosis (scleroderma).Springer seminars in immunopathology · 1999Review
Corrections and comments
- Retraction · 2003-10-15Falsification/Fabrication of Data · Investigation by Company/Institution · Investigation by Third Party · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author ·
- RetractedRetraction.2003
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The products of the collagen-alpha 1(I) and -alpha 2(I) genes form the triple helical molecule collagen type I, which constitutes the major ECM protein in tissue fibrosis. The collagen-alpha 1(I) gene is mainly transcriptionally regulated, and its promoter activity depends on the interaction of the transcription factors NF-I and Sp1 with a tandem repeat of evolutionary conserved NF-I/Sp1 switch elements. An increased affinity of Sp1 to these elements has been observed in experimental liver fibrosis. Here, we demonstrate that the DNA binding drug mithramycin displays a high affinity binding to the GC-rich elements in the collagen-alpha 1(I) promoter as measured by DNAse I protection and gel retardation assays. Mithramycin interferes with Sp1 but not with NF-I binding to these sites. At a concentration of 100 nM, mithramycin efficiently reduces basal and TGF-beta-stimulated alpha 1(I) gene expression in human primary fibroblasts. The transcriptional activity and mRNA steady state levels of other genes, including the collagenase gene, as well as the growth rate of fibroblasts remained unchanged on exposure to this drug. Taken together, our results indicate that the transcriptional activity of the type I collagen gene highly depends on its GC-rich regulatory elements, and further, that these elements can be differentially blocked, thereby changing the balance between ECM structural and degrading gene activities in human fibroblasts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.