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

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 i...

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Bibliographic Details
Published in:PloS one 2019-09, Vol.14 (9), p.e0222869
Main Authors: Kitanaka, Nanako, Nakano, Rei, Sakai, Manabu, Kitanaka, Taku, Namba, Shinichi, Konno, Tadayoshi, Nakayama, Tomohiro, Sugiya, Hiroshi
Format: Article
Language:English
Subjects:
Analysis
Cellular signal transduction
Cytokines
EDTA
Extracellular matrix
Fibroblasts
Interleukins
Messenger RNA
Proteins
RNA
Wound care
Wound healing
Wounds
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Summary: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-1[beta] (IL-1[beta], 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-1[beta]-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-1[beta]-induced MMP-3 mRNA expression was reduced. We also demonstrated that IL-1[beta] stimulates the phosphorylation of ATF-2. These observations suggest that ATF-2 plays an important role in IL-1[beta]-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-1[beta]-induced MMP-3 mRNA expression was reduced. In addition, we showed that IL-1[beta] induced the phosphorylation of ERK1/2. These observations suggest that ERK1 and ERK2 are involved in IL-1[beta]-induced MMP-3 expression. However, ERK1 and ERK2 do seem to play different roles. While the ERK inhibitor FR180204 inhibited IL-1[beta]-induced ATF-2 phosphorylation, only in cells transfected with ERK1 siRNA, but not ERK2 siRNA, IL-1[beta]-induced ATF-2 phosphorylation was reduced. These findings suggest that the ERK1/ATF-2 signaling axis contributes to IL-1[beta]-induced MMP-3 expression in dermal fibroblasts.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0222869