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02950nam a2200589Ia 4500 |
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10.1177-0022034518775971 |
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220706s2018 CNT 000 0 und d |
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|a 00220345 (ISSN)
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|a Multiple Functions of Lysyl Oxidase Like-2 in Oral Fibroproliferative Processes
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|b SAGE Publications Inc.
|c 2018
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|z View Fulltext in Publisher
|u https://doi.org/10.1177/0022034518775971
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|a Gingival overgrowth is a side effect of certain medications, including calcium channel blockers, cyclosporin A, and phenytoin. Phenytoin-induced gingival overgrowth is fibrotic. Lysyl oxidases are extracellular enzymes that are required for biosynthetic cross-linking of collagens, and members of this enzyme family are upregulated in fibrosis. Previous studies in humans and in a mouse model of phenytoin-induced gingival overgrowth have shown that LOXL2 is elevated in the epithelium and connective tissue in gingival overgrowth tissues and not in normal tissues. Here, using a novel LOXL2 isoform-selective inhibitor and knockdown studies in loss- and gain-of-function studies, we investigated roles for LOXL2 in promoting cultures of human gingival fibroblasts to proliferate and to accumulate collagen. Data indicate that LOXL2 stimulates gingival fibroblast proliferation, likely by a platelet-derived growth factor B receptor-mediated mechanism. Moreover, collagen accumulation was stimulated by LOXL2 enzyme and inhibited by LOXL2 inhibitor or gene knockdown. These studies suggest that LOXL2 could serve as a potential therapeutic target to address oral fibrotic conditions. © International & American Associations for Dental Research 2018.
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|a adult
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|a Adult
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|a Amino Acid Oxidoreductases
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|a Blotting, Western
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|a cell biology
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|a cell culture
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|a cell proliferation
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|a Cell Proliferation
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|a Cells, Cultured
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|a collagen
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|a Collagen
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|a extracellular matrix
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|a female
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|a Female
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|a fibroblast
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|a fibroblasts
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|a Fibroblasts
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|a gene knockdown
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|a Gene Knockdown Techniques
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|a gingiva
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|a Gingiva
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|a growth, development and aging
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|a human
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|a Humans
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|a LOXL2 protein, human
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|a matrix biology
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|a metabolism
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|a oxidoreductase
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|a physiology
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|a platelet derived growth factor beta receptor
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|a Receptor, Platelet-Derived Growth Factor beta
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|a receptors
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|a Western blotting
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|a Findlay, A.D.
|e author
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|a Kantarci, A.
|e author
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|a Mahjour, F.
|e author
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|a Mously, E.A.
|e author
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|a Saxena, D.
|e author
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|a Trackman, P.C.
|e author
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|t Journal of Dental Research
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