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• W2120018818 endingPage "C590" @default.
• W2120018818 startingPage "C581" @default.
• W2120018818 abstract "Connective tissue growth factor (CCN2/CTGF) mediates transforming growth factor-β (TGF-β)-induced fibrosis. Drug-induced gingival overgrowth is tissue specific. Here the role of the phosphoinositol 3-kinase (PI3K) pathway in mediating TGF-β1-stimulated CCN2/CTGF expression in primary human adult gingival fibroblasts and human adult lung fibroblasts was compared. Data indicate that PI3K inhibitors attenuate upregulation of TGF-β1-induced CCN2/CTGF expression in human gingival fibroblasts independent of reducing JNK MAP kinase activation. Pharmacologic inhibitors and small interfering (si)RNA-mediated knockdown studies indicate that calcium-dependent isoforms and an atypical isoform of protein kinase C (PKC-δ) do not mediate TGF-β1-stimulated CCN2/CTGF expression in gingival fibroblasts. As glycogen synthase kinase-3β (GSK-3β) can undergo phosphorylation by the PI3K/pathway, the effects of GSK-3β inhibitor kenpaullone and siRNA knockdown were investigated. Data in gingival fibroblasts indicate that kenpaullone attenuates TGF-β1-mediated CCN2/CTGF expression. Activation of the Wnt canonical pathways with Wnt3a, which inhibits GSK-3β, similarly inhibits TGF-β1-stimulated CCN2/CTGF expression. In contrast, inhibition of GSK-3β by Wnt3a does not inhibit, but modestly stimulates, CCN2/CTGF levels in primary human adult lung fibroblasts and is β-catenin dependent, consistent with previous studies performed in other cell models. These data identify a novel pathway in gingival fibroblasts in which inhibition of GSK-3β attenuates CCN2/CTGF expression. In adult lung fibroblasts inhibition of GSK-3β modestly stimulates TGF-β1-regulated CCN2/CTGF expression. These studies have potential clinical relevance to the tissue specificity of drug-induced gingival overgrowth." @default.
• W2120018818 created "2016-06-24" @default.
• W2120018818 creator A5005159111 @default.
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• W2120018818 creator A5037338684 @default.
• W2120018818 creator A5068260159 @default.
• W2120018818 date "2013-09-15" @default.
• W2120018818 modified "2023-09-24" @default.
• W2120018818 title "Requirement for active glycogen synthase kinase-3β in TGF-β₁upregulation of connective tissue growth factor (CCN2/CTGF) levels in human gingival fibroblasts" @default.
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• W2120018818 doi "https://doi.org/10.1152/ajpcell.00032.2013" @default.
• W2120018818 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3761177" @default.
• W2120018818 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23824844" @default.
• W2120018818 hasPublicationYear "2013" @default.
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