Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases
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 ant...
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BMC
2020-09-01
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Series: | BMC Nephrology |
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Online Access: | http://link.springer.com/article/10.1186/s12882-020-02060-9 |
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author | Ayano Kubo Teruo Hidaka Maiko Nakayama Yu Sasaki Miyuki Takagi Hitoshi Suzuki Yusuke Suzuki |
author_facet | Ayano Kubo Teruo Hidaka Maiko Nakayama Yu Sasaki Miyuki Takagi Hitoshi Suzuki Yusuke Suzuki |
author_sort | Ayano Kubo |
collection | DOAJ |
description | 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-1-prolyl-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. |
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issn | 1471-2369 |
language | English |
last_indexed | 2024-12-21T17:45:29Z |
publishDate | 2020-09-01 |
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spelling | doaj.art-1c7b87f075d9458bb2434535e662435f2022-12-21T18:55:31ZengBMCBMC Nephrology1471-23692020-09-0121111410.1186/s12882-020-02060-9Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseasesAyano Kubo0Teruo Hidaka1Maiko Nakayama2Yu Sasaki3Miyuki Takagi4Hitoshi Suzuki5Yusuke Suzuki6Department of Nephrology, Juntendo University Faculty of MedicineDepartment of Nephrology, Juntendo University Faculty of MedicineDepartment of Nephrology, Juntendo University Faculty of MedicineDepartment of Nephrology, Juntendo University Faculty of MedicineDepartment of Nephrology, Juntendo University Faculty of MedicineDepartment of Nephrology, Juntendo University Faculty of MedicineDepartment of Nephrology, Juntendo University Faculty of MedicineAbstract 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-1-prolyl-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.http://link.springer.com/article/10.1186/s12882-020-02060-9DPP-4PodocyteGlomerular diseaseSynaptopodinSaxagliptin |
spellingShingle | Ayano Kubo Teruo Hidaka Maiko Nakayama Yu Sasaki Miyuki Takagi Hitoshi Suzuki Yusuke Suzuki Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases BMC Nephrology DPP-4 Podocyte Glomerular disease Synaptopodin Saxagliptin |
title | Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases |
title_full | Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases |
title_fullStr | Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases |
title_full_unstemmed | Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases |
title_short | Protective effects of DPP-4 inhibitor on podocyte injury in glomerular diseases |
title_sort | protective effects of dpp 4 inhibitor on podocyte injury in glomerular diseases |
topic | DPP-4 Podocyte Glomerular disease Synaptopodin Saxagliptin |
url | http://link.springer.com/article/10.1186/s12882-020-02060-9 |
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