RRC ID 36780
Author Higashijima Y, Tanaka T, Yamaguchi J, Tanaka S, Nangaku M.
Title Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury.
Journal 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.
Volume 308(8)
Pages F878-87
Published 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 3.323
Times Cited 38
Human and Animal Cells RAW 264(RCB0535)