ERK1/ATF-2 signaling axis contributes to interleukin-1β-induced MMP-3 expression in dermal fibroblasts

Autoři: Nanako Kitanaka aff001;  Rei Nakano aff001;  Manabu Sakai aff003;  Taku Kitanaka aff001;  Shinichi Namba aff001;  Tadayoshi Konno aff001;  Tomohiro Nakayama aff004;  Hiroshi Sugiya aff001
Působiště autorů: Laboratories of Veterinary Biochemistry, 3 Veterinary Internal Medicine, and 4Veterinary Radiotherapy, Nihon University College of Bioresource Sciences, Kameino, Fujisawa, Kanagawa, Japan aff001;  Laboratory for Cellular Function Conversion Technology, RIKEN Center for Integrative Medical Sciences, Suehiro-cho, Tsurumi, Yokohama, Kanagawa, Japan aff002;  Laboratories of Veterinary Internal Medicine, Nihon University College of Bioresource Sciences, Kameino, Fujisawa, Kanagawa, Japan aff003;  Laboratories of Veterinary Radiotherapy, Nihon University College of Bioresource Sciences, Kameino, Fujisawa, Kanagawa, Japan aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222869


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.

Klíčová slova:

Biology and life sciences – Cell biology – Cellular types – Animal cells – Connective tissue cells – Fibroblasts – Signal transduction – Cell signaling – Signaling cascades – MAPK signaling cascades – Cell motility – Cell migration – Anatomy – Biological tissue – Connective tissue – Genetics – Gene expression – Gene regulation – Small interfering RNAs – Biochemistry – Nucleic acids – RNA – Non-coding RNA – Proteins – Post-translational modification – Phosphorylation – DNA-binding proteins – Transcription factors – Regulatory proteins – Physiology – Physiological processes – Tissue repair – Wound healing – Developmental biology – Molecular biology – Molecular biology techniques – Transfection – Medicine and health sciences – Research and analysis methods


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