PloS one, 2019-09, Vol.14 (9), p.e0222869-e0222869
2019
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- Autor(en) / Beteiligte
- Titel
- ERK1/ATF-2 signaling axis contributes to interleukin-1β-induced MMP-3 expression in dermal fibroblasts
- Ist Teil von
- PloS one, 2019-09, Vol.14 (9), p.e0222869-e0222869
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- Matrix metalloproteinases (MMPs) play a pivotal role in tissue remodeling by degrading the extracellular matrix (ECM) components. This mechanism is implicated in a variety of physiological and pathological cellular processes including wound healing. One of the key proteins involved in this process is the proinflammatory cytokine interleukin-1β (IL-1β, which induces the expression of MMP-3 mRNA and the secretion of MMP-3 protein by dermal fibroblasts. In this study, we first investigated the contribution of activating transcription factor 2 (ATF-2) to IL-1β-induced MMP-3 expression in dermal fibroblasts. Our results showed that in cells transfected with ATF-2 siRNA or treated with the ATF-2 inhibitor SBI-0087702, IL-1β-induced MMP-3 mRNA expression was reduced. We also demonstrated that IL-1β stimulates the phosphorylation of ATF-2. These observations suggest that ATF-2 plays an important role in IL-1β-induced MMP-3 expression. Next, we investigated the role of MAPK signaling in ATF-2 activation. In cells treated with the extracellular signal-regulated kinase (ERK) inhibitor FR180240, as well as in cells transfected with ERK1 and ERK2 siRNAs, IL-1β-induced MMP-3 mRNA expression was reduced. In addition, we showed that IL-1β induced the phosphorylation of ERK1/2. These observations suggest that ERK1 and ERK2 are involved in IL-1β-induced MMP-3 expression. However, ERK1 and ERK2 do seem to play different roles. While the ERK inhibitor FR180204 inhibited IL-1β-induced ATF-2 phosphorylation, only in cells transfected with ERK1 siRNA, but not ERK2 siRNA, IL-1β-induced ATF-2 phosphorylation was reduced. These findings suggest that the ERK1/ATF-2 signaling axis contributes to IL-1β-induced MMP-3 expression in dermal fibroblasts.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0222869Titel-ID: cdi_plos_journals_2294170916
- Format
- –
- Schlagworte
- Activating transcription factor 2, Activating Transcription Factor 2 - genetics, Activating Transcription Factor 2 - metabolism, Animals, Biochemistry, Biology and Life Sciences, Cancer, Cell activation, Cell cycle, Cells, Cultured, Cytokines, Dermis - cytology, Dogs, Enzyme inhibitors, Extracellular matrix, Extracellular signal-regulated kinase, Fibroblasts, Fibroblasts - cytology, Fibroblasts - drug effects, Fibroblasts - metabolism, Fluorides, Gene expression, Gene Expression Regulation, Enzymologic - drug effects, Growth factors, IL-1β, Inflammation, Inhibitors, Interleukin-1beta - pharmacology, Interleukins, Internal medicine, Kinases, Laboratories, Male, MAP kinase, Matrix metalloproteinase, Matrix Metalloproteinase 3 - genetics, Matrix Metalloproteinase 3 - metabolism, Matrix metalloproteinases, Medicine, Medicine and Health Sciences, Mitogen-Activated Protein Kinase 1 - genetics, Mitogen-Activated Protein Kinase 1 - metabolism, Mitogen-Activated Protein Kinase 3 - genetics, Mitogen-Activated Protein Kinase 3 - metabolism, Phosphorylation, Proteins, Radiation therapy, Research and Analysis Methods, RNA Interference, Signal transduction, Signal Transduction - drug effects, Signal Transduction - genetics, Signaling, siRNA, Skin, Stromelysin 1, Wound healing