RRC ID 45085
著者 Maeda-Sano K, Gotoh M, Morohoshi T, Someya T, Murofushi H, Murakami-Murofushi K.
タイトル Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts.
ジャーナル Biochim Biophys Acta
Abstract Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway.
巻・号 1841(9)
ページ 1256-63
公開日 2014-9-1
DOI 10.1016/j.bbalip.2014.05.004
PII S1388-1981(14)00095-X
PMID 24845645
MeSH Cell Line Cyclic AMP Response Element-Binding Protein / genetics* Cyclic AMP Response Element-Binding Protein / metabolism Dose-Response Relationship, Drug Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism Fibroblasts / cytology Fibroblasts / drug effects* Fibroblasts / metabolism GTP-Binding Protein alpha Subunits, Gi-Go / genetics GTP-Binding Protein alpha Subunits, Gi-Go / metabolism Gene Expression Regulation Glucuronosyltransferase / genetics Glucuronosyltransferase / metabolism Heterocyclic Compounds, 1-Ring / pharmacology* Humans Hyaluronan Synthases Hyaluronic Acid / agonists Hyaluronic Acid / biosynthesis* Lysophospholipids / pharmacology* Phosphatidic Acids / pharmacology* Phosphatidylinositol 3-Kinase / genetics Phosphatidylinositol 3-Kinase / metabolism Receptors, Lysophosphatidic Acid / genetics Receptors, Lysophosphatidic Acid / metabolism Signal Transduction Skin / cytology Skin / drug effects* Skin / metabolism
IF 3.411
引用数 18
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 NB1RGB(RCB0222)