論文 - 詳細
| RRC ID | 52292 |
|---|---|
| 著者 | Tsushima H, Morimoto S, Fujishiro M, Yoshida Y, Hayakawa K, Hirai T, Miyashita T, Ikeda K, Yamaji K, Takamori K, Takasaki Y, Sekigawa I, Tamura N. |
| タイトル | Kinase inhibitors of the IGF-1R as a potential therapeutic agent for rheumatoid arthritis. |
| ジャーナル | Autoimmunity |
| Abstract |
We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA. |
| 巻・号 | 50(5) |
| ページ | 329-335 |
| 公開日 | 2017-8-1 |
| DOI | 10.1080/08916934.2017.1344970 |
| PMID | 28682648 |
| MeSH | Animals Antirheumatic Agents / pharmacology* Antirheumatic Agents / therapeutic use Arthritis, Rheumatoid / drug therapy Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology Cell Line Cell Proliferation / drug effects Female Humans Insulin-Like Growth Factor I / metabolism Insulin-Like Growth Factor I / pharmacology Macrophage Colony-Stimulating Factor / metabolism Macrophage Colony-Stimulating Factor / pharmacology Mice Neovascularization, Pathologic / metabolism Osteoclasts / cytology Osteoclasts / drug effects Osteoclasts / metabolism Protein Kinase Inhibitors / pharmacology* Protein Kinase Inhibitors / therapeutic use Pyrimidines / pharmacology Pyrroles / pharmacology RANK Ligand / metabolism RANK Ligand / pharmacology Receptor, IGF Type 1 Receptors, Somatomedin / antagonists & inhibitors* Receptors, Somatomedin / metabolism* Signal Transduction / drug effects |
| IF | 2.125 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |