PMID- 30056058 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20190215 IS - 1095-9319 (Electronic) IS - 0026-2862 (Linking) VI - 120 DP - 2018 Nov TI - Advanced glycation end products evoke inflammatory reactions in proximal tubular cells via autocrine production of dipeptidyl peptidase-4. PG - 90-93 LID - S0026-2862(18)30040-2 [pii] LID - 10.1016/j.mvr.2018.07.004 [doi] AB - We have previously shown that albuminuria and renal levels of advanced glycation end products (AGEs), receptor for AGEs (RAGE), and oxidative stress are suppressed in dipeptidyl peptidase-4 (DPP-4)-deficient diabetic rats, thus suggesting the crosstalk between AGE-RAGE axis and DPP-4 in experimental diabetic nephropathy. Therefore, we examined here the role of DPP-4 in AGE-evoked inflammatory reactions in human proximal tubular cells. Proteins were extracted from proximal tubular cells, and conditioned medium was collected, both of which were subjected to western blot analysis using anti-DPP-4 antibody. RAGE-aptamer was prepared using a systemic evolution of ligands by exponential enrichment. NF-kappaB p65 and monocyte chemoattractant protein-1 (MCP-1) gene expression was analyzed by reverse transcription-polymerase chain reaction. AGEs significantly increased DPP-4 expression and soluble DPP-4 production by tubular cells, the latter of which was attenuated by RAGE-aptamer or an anti-oxidant, N-acetylcysteine. AGEs or DPP-4 up-regulated NF-kappaB p65 or MCP-1 mRNA levels in tubular cells, which were suppressed by linagliptin, an inhibitor of DPP-4. AGEs stimulated NF-kappaB p65 gene expression in tubular cells isolated from control rats, but not from DPP-4-deficient rats. Our present results suggest that the AGE-RAGE-mediated oxidative stress could evoke inflammatory reactions in proximal tubular cells via autocrine production of DPP-4. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Kaifu, Kumiko AU - Kaifu K AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Ueda, Seiji AU - Ueda S AD - Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan. FAU - Nakamura, Nobutaka AU - Nakamura N AD - Department Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. FAU - Matsui, Takanori AU - Matsui T AD - Department Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. FAU - Yamada-Obara, Nana AU - Yamada-Obara N AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Ando, Ryotaro AU - Ando R AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Kaida, Yusuke AU - Kaida Y AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Nakata, Masami AU - Nakata M AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan. FAU - Matsukuma-Toyonaga, Maki AU - Matsukuma-Toyonaga M AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Higashimoto, Yuichiro AU - Higashimoto Y AD - Department of Chemistry, Kurume University School of Medicine, Kurume, Japan. FAU - Fukami, Kei AU - Fukami K AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Suzuki, Yusuke AU - Suzuki Y AD - Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan. FAU - Okuda, Seiya AU - Okuda S AD - Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Yamagishi, Sho-Ichi AU - Yamagishi SI AD - Department Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. Electronic address: shoichi@med.kurume-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180726 PL - United States TA - Microvasc Res JT - Microvascular research JID - 0165035 RN - 0 (AGER protein, human) RN - 0 (Ager protein, rat) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Glycation End Products, Advanced) RN - 0 (Inflammation Mediators) RN - 0 (RELA protein, human) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Rela protein, rat) RN - 0 (Transcription Factor RelA) RN - 0 (advanced glycation end products-bovine serum albumin) RN - 27432CM55Q (Serum Albumin, Bovine) RN - EC 3.4.14.5 (DPP4 protein, human) RN - EC 3.4.14.5 (DPP4 protein, rat) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) SB - IM MH - Animals MH - Autocrine Communication/*drug effects MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Dipeptidyl Peptidase 4/deficiency/genetics/*metabolism MH - Glycation End Products, Advanced/*toxicity MH - Humans MH - Inflammation Mediators/*metabolism MH - Kidney Tubules, Proximal/*drug effects/enzymology/pathology MH - Male MH - Oxidative Stress/drug effects MH - Rats, Inbred F344 MH - Rats, Sprague-Dawley MH - Rats, Transgenic MH - Receptor for Advanced Glycation End Products/agonists/metabolism MH - Serum Albumin, Bovine/*toxicity MH - Signal Transduction/drug effects MH - Transcription Factor RelA/genetics/metabolism OTO - NOTNLM OT - AGEs OT - DPP-4 OT - Diabetic nephropathy OT - Inflammation OT - Proximal tubular cells EDAT- 2018/07/30 06:00 MHDA- 2019/02/05 06:00 CRDT- 2018/07/30 06:00 PHST- 2018/02/28 00:00 [received] PHST- 2018/07/25 00:00 [revised] PHST- 2018/07/26 00:00 [accepted] PHST- 2018/07/30 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2018/07/30 06:00 [entrez] AID - S0026-2862(18)30040-2 [pii] AID - 10.1016/j.mvr.2018.07.004 [doi] PST - ppublish SO - Microvasc Res. 2018 Nov;120:90-93. doi: 10.1016/j.mvr.2018.07.004. Epub 2018 Jul 26.