SynopsisMatrix metalloproteinases degrade the extracellular matrix during remodeling, and their activity is regulated by tissue metalloproteinase inhibitors (TIMPs). Platelet-derived growth factor (PDGF) is produced in periodontal tissue and is an important regulator of wound healing and tissue repair. ERK1/2, members of the MAPK family, are intracellular signaling substance kinases involved in TIMP-1 production. To elucidate the mechanisms underlying connective tissue remodeling, the present study investigated the relationship between PDGF-bb-stimulated TIMP-1 production and ERK1/2 phosphorylation in human gingival fibroblasts (HGF). TIMP-1 production increased in a PDGF-bb concentration-dependent manner. PDGF-bb-induced increases in TIMP-1 were further enhanced by the p38α/β inhibitor SB239063 and p38α-siRNA. The PDGF-bb stimulation also induced the phosphorylation of ERK1/2. In contrast, the treatment with the p38-MAPK inhibitor SB203580 suppressed the phosphorylation of ERK1/2. These results suggest that PDGF-bb induced the production of TIMP-1 through the ERK1/2-activated signal transduction pathway in HGF. In addition, signaling cross-talk between p38α and ERK1/2 was involved in ERK1/2 activation, suggesting that ERK1/2 activation is coordinately regulated by p38α.
Key words: PDGF-bb, TIMP-1, human gingival fibroblasts
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DOI :
"https://doi.org/10.11344/nano.15.44"
J-stage :
Morisaki A, Inoue H, Goda S. Effects of platelet-derived growth factor-bb on tissue inhibitor of metalloproteinase-1 production in human gingival-derived fibroblasts. Nano Biomed 2023; 15: 44-50.
