Maqbool, A, Hemmings, KE, O'Regan, DJ et al. (3 more authors) (2013) Interleukin-1 has opposing effects on connective tissue growth factor and tenascin-C expression in human cardiac fibroblasts. Matrix Biology, 32 (3-4). 208 - 214. ISSN 0945-053X
Abstract
Cardiac fibroblasts (CF) play a central role in the repair and remodeling of the heart following injury and are important regulators of inflammation and extracellular matrix (ECM) turnover. ECM-regulatory matricellular proteins are synthesized by several myocardial cell types including CF. We investigated the effects of pro-inflammatory cytokines on matricellular protein expression in cultured human CF. cDNA array analysis of matricellular proteins revealed that interleukin-1α (IL-1α, 10ng/ml, 6h) down-regulated connective tissue growth factor (CTGF/CCN2) mRNA by 80% and up-regulated tenascin-C (TNC) mRNA levels by 10-fold in human CF, without affecting expression of thrombospondins 1-3, osteonectin or osteopontin. Western blotting confirmed these changes at the protein level. In contrast, tumor necrosis factor α (TNFα) did not modulate CCN2 expression and had only a modest stimulatory effect on TNC levels. Signaling pathway inhibitor studies suggested an important role for the p38 MAPK pathway in suppressing CCN2 expression in response to IL-1α. In contrast, multiple signaling pathways (p38, JNK, PI3K/Akt and NFκB) contributed to IL-1α-induced TNC expression. In conclusion, IL-1α reduced CCN2 expression and increased TNC expression in human CF. These observations are of potential value for understanding how inflammation and ECM regulation are linked at the level of the CF.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | NOTICE: this is the author’s version of a work that was accepted for publication in Matrix Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Matrix Biology, 32 (3-4), 2013, 10.1016/j.matbio.2013.02.003 |
Keywords: | Cells, cultured; Connective tissue growth factor; Gene expression; Gene expression regulation; Humans; Interleukin-1alpha; Myocardium; Myofibroblasts; Phenotype; RNA, messenger; Signal transduction; Tenascin; Tumor necrosis factor-alpha; Cardiac fibroblasts; Tenascin-C |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Feb 2014 10:51 |
Last Modified: | 15 Sep 2014 01:57 |
Published Version: | http://dx.doi.org/10.1016/j.matbio.2013.02.003 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.matbio.2013.02.003 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:77823 |