論文 - 詳細
| RRC ID | 36780 |
|---|---|
| 著者 | Higashijima Y, Tanaka T, Yamaguchi J, Tanaka S, Nangaku M. |
| タイトル | Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. |
| ジャーナル | Am J Physiol Renal Physiol |
| Abstract |
Dipeptidyl peptidase (DPP)-4 is an enzyme that cleaves and inactivates incretin hormones capable of stimulating insulin secretion from pancreatic β-cells. DPP-4 inhibitors are now widely used for the treatment of type 2 diabetes. Experimental studies have suggested a renoprotective role of DPP-4 inhibitors in various models of diabetic kidney disease, which may be independent of lowering blood glucose levels. In the present study, we examined the effect of DPP-4 inhibitors in the rat Thy-1 glomerulonephritis model, a nondiabetic glomerular injury model. Rats were injected with OX-7 (1.2 mg/kg iv) and treated with the DPP-4 inhibitor alogliptin (20 mg·kg(-1)·day(-1)) or vehicle for 7 days orally by gavage. Alogliptin significantly reduced the number of CD68-positive inflammatory macrophages in the kidney, which was associated with a nonsignificant tendency to ameliorate glomerular injury and reduce proteinuria. Another DPP-4 inhibitor, anagliptin (300 mg·kg(-1)·day(-1) mixed with food) and a glucagon-like peptide-1 receptor agonist, exendin-4 (10 mg/kg sc), similarly reduced CD68-positive macrophage infiltration to the kidney. Furthermore, ex vivo transmigration assays using peritoneal macrophages revealed that exendin-4, but not alogliptin, dose dependently reduced monocyte chemotactic protein-1-stimulated macrophage infiltration. These data suggest that DPP-4 inhibitors reduced macrophage infiltration directly via glucagon-like peptide-1-dependent signaling in the rat Thy-1 nephritis model and indicate that the control of inflammation by DPP-4 inhibitors is useful for the treatment of nondiabetic kidney disease models. |
| 巻・号 | 308(8) |
| ページ | F878-87 |
| 公開日 | 2015-4-15 |
| DOI | 10.1152/ajprenal.00590.2014 |
| PII | ajprenal.00590.2014 |
| PMID | 25656369 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology* Antigens, CD / metabolism Antigens, Differentiation, Myelomonocytic / metabolism Antilymphocyte Serum Cell Line Chemokine CCL2 / pharmacology Chemotaxis / drug effects Cytoprotection Dipeptidyl Peptidase 4 / metabolism* Dipeptidyl-Peptidase IV Inhibitors / pharmacology* Disease Models, Animal Exenatide Glomerulonephritis / enzymology Glomerulonephritis / immunology Glomerulonephritis / pathology Glomerulonephritis / prevention & control* Glucagon-Like Peptide-1 Receptor Kidney Glomerulus / drug effects* Kidney Glomerulus / enzymology Kidney Glomerulus / immunology Kidney Glomerulus / pathology Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / immunology Male Mice, Inbred C57BL Peptides / pharmacology Piperidines / pharmacology* Proteinuria / enzymology Proteinuria / immunology Proteinuria / prevention & control Pyrimidines / pharmacology* Rats, Sprague-Dawley Receptors, Glucagon / agonists Receptors, Glucagon / metabolism Signal Transduction / drug effects Uracil / analogs & derivatives* Uracil / pharmacology Venoms / pharmacology |
| IF | 3.191 |
| 引用数 | 38 |
| WOS 分野 | PHYSIOLOGY UROLOGY & NEPHROLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 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 | RAW 264(RCB0535) |