Multiple Functions of Lysyl Oxidase Like-2 in Oral Fibroproliferative Processes
| Autor: | Mously Ea, Philip C. Trackman, Saxena D, Findlay Ad, Alpdogan Kantarci, Faranak Mahjour |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_treatment Blotting Western Gingiva Connective tissue Lysyl oxidase Extracellular matrix Receptor Platelet-Derived Growth Factor beta 03 medical and health sciences Fibrosis Cyclosporin a medicine Humans General Dentistry Cells Cultured Cell Proliferation LOXL2 Chemistry Growth factor Research Reports Fibroblasts medicine.disease Epithelium 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques Cancer research Female Amino Acid Oxidoreductases Collagen |
| Zdroj: | Journal of dental research. 97(11) |
| ISSN: | 1544-0591 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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