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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | O'reilly, Steven Van Laar, Jacob M. Ciechomska, Marzena Cant, Rachel |
| Description | Author Affiliation: O'Reilly S ( From the Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.) |
| Abstract | Fibrosis is a common and intractable condition associated with various pathologies. It is characterized by accumulation of an excessive amount of extracellular matrix molecules that primarily include collagen type I. IL-6 is a profibrotic cytokine that is elevated in the prototypic fibrotic autoimmune condition systemic sclerosis and is known to induce collagen I expression, but the mechanism(s) behind this induction are currently unknown. Using healthy dermal fibroblasts in vitro, we analyzed the signaling pathways that underscore the IL-6-mediated induction of collagen. We show that IL-6 trans signaling is important and that the effect is dependent on STAT3; however, the effect is indirect and mediated through enhanced TGF-ß signaling and the classic downstream cellular mediator Smad3. This is due to induction of the bone morphogenetic protein (BMP) antagonist Gremlin-1, and we show that Gremlin-1 is profibrotic and is mediated through canonical TGF-ß signaling. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 14 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-04-04 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Fibroblasts Metabolism Intercellular Signaling Peptides And Proteins Interleukin-6 STAT3 Transcription Factor Signal Transduction Smad3 Protein Transforming Growth Factor Beta Bone Morphogenetic Proteins Biosynthesis Genetics Cells, Cultured Collagen Type I Pathology Fibrosis Clinical Trial Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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