Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases
- PDF / 2,482,871 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 70 Downloads / 150 Views
RESEARCH ARTICLE
Open Access
Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases Ayano Kubo1, Teruo Hidaka1, Maiko Nakayama1, Yu Sasaki1, Miyuki Takagi1, Hitoshi Suzuki1,2 and Yusuke Suzuki1*
Abstract Background: Dipeptidyl peptidase-4 (DPP-4) is a serine protease that inhibits the degradation of glucagon-like peptide 1. DPP-4 inhibitors are used worldwide to treat type 2 diabetes mellitus and were recently shown to have pleiotropic effects such as anti-oxidant, anti-inflammatory, and anti-fibrotic actions. DPP-4 inhibitors improve albuminuria and renal injury including glomerular damage independent of its hypoglycemic effect. Although DPP-4 is mainly expressed in the kidney, the physiological function of DPP-4 remains unclear. Methods: The localization of renal DPP-4 activity was determined in human renal biopsy specimens with glycyl-1prolyl-4-methoxy-2-naphthylamide and the effects of a DPP-4 inhibitor were examined in human cultured podocyte. Results: DPP-4 activity under normal conditions was observed in some Bowman’s capsular epithelial cells and proximal tubules, but not in the glomerulus. DPP-4 activity was observed in crescent formation in anti-neutrophil myeloperoxidase cytoplasmic antigen antibody nephritis, nodular lesions in diabetic nephropathy, and some podocytes in focal segmental glomerulosclerosis. Notably, the DPP-4 inhibitor saxagliptin suppressed DPP-4 activity in podocytes and the proximal tubules. To assess the effect of DPP-4 inhibitor on podocytes, human cultured podocytes were injured by Adriamycin, which increased DPP-4 activity; this activity was dose-dependently suppressed by saxagliptin. Treatment with saxagliptin maintained the structure of synaptopodin and RhoA. Saxagliptin also improved the detachment of podocytes. Conclusions: DPP-4 activity induces degradation of synaptopodin and reduction of RhoA, resulting in destruction of the podocyte cytoskeleton. Saxagliptin may have pleiotropic effects to prevent podocyte injury. Keywords: DPP-4, Podocyte, Glomerular disease, Synaptopodin, Saxagliptin
Background Dipeptidyl peptidase-4 (DPP-4) is a serine protease that exists in membrane-bound or soluble forms. The catalytic activity of DPP-4 removes the N-terminal dipeptide from peptides containing proline or alanine at the second position. The soluble form degrades glucagon-like peptide 1 (GLP-1), which is an incretin hormone secreted from the gastrointestinal tract in response to food intake. The active form of GLP-1 stimulates insulin * Correspondence: [email protected] 1 Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Full list of author information is available at the end of the article
secretion in a blood glucose-dependent manner. The active form of GLP-1 is rapidly degraded and inactivated by DPP-4. Therefore, DPP-4 inhibitors have hypoglycemic effects by inhibiting the degradation of GLP-1 in patients with type 2 diabetes mellitus [1]. However, the physiological role of DPP-4 remain
Data Loading...
