Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production. In vitro findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.

Citations

Citations to this article as recorded by  

• Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis
  Birte Ohm, Isabelle Moneke, Wolfgang Jungraithmayr
  British Journal of Pharmacology.2023; 180(22): 2846.     CrossRef
• Linagliptin ameliorates pulmonary fibrosis in systemic sclerosis mouse model via inhibition of endothelial-to-mesenchymal transition
  Biwei Pei, Na Zhang, Tingting Pang, Gengyun Sun
  Molecular and Cellular Biochemistry.2022; 477(4): 995.     CrossRef
• Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes
  Yewon Na, Soo Wan Kim, Ie Byung Park, Soo Jung Choi, Seungyoon Nam, Jaehun Jung, Dae Ho Lee
  The Journal of Clinical Endocrinology & Metabolism.2022; 107(11): 3022.     CrossRef
• Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells
  Hye-Young Seo, So-Hee Lee, Eugene Han, Jae Seok Hwang, Sol Han, Mi Kyung Kim, Byoung Kuk Jang
  International Journal of Molecular Sciences.2022; 23(19): 11636.     CrossRef
• Optimization and validation of a fluorogenic dipeptidyl peptidase 4 enzymatic assay in human plasma
  Hyunyee Yoon, Su Hee Cho, Yu Rim Seo, Kyung-Sang Yu, Sung Sup Park, Moon Jung Song
  Analytical Biochemistry.2021; 612: 113952.     CrossRef
• Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside
  Sungjin Chung, Gheun-Ho Kim
  Life.2021; 11(5): 389.     CrossRef
• Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?
  Xin Huang, Yimin Khoong, Chengyao Han, Dai Su, Hao Ma, Shuchen Gu, Qingfeng Li, Tao Zan
  Frontiers in Physiology.2021;[Epub]     CrossRef
• Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active‐controlled, randomized, double‐blind study with open‐label extension (the EVERGREEN study)
  Gyuri Kim, Soo Lim, Hyuk‐Sang Kwon, Ie B. Park, Kyu J. Ahn, Cheol‐Young Park, Su K. Kwon, Hye S. Kim, Seok W. Park, Sin G. Kim, Min K. Moon, Eun S. Kim, Choon H. Chung, Kang S. Park, Mikyung Kim, Dong J. Chung, Chang B. Lee, Tae H. Kim, Moon‐Kyu Lee
  Diabetes, Obesity and Metabolism.2020; 22(9): 1527.     CrossRef

• Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus

  
  Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
  Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 4113.     CrossRef
• Efficacy and safety of novel dipeptidyl-peptidase-4 inhibitor evogliptin in the management of type 2 diabetes mellitus: A meta-analysis
  Deep Dutta, Saptarshi Bhattacharya, Aishwarya Krishnamurthy, LokeshKumar Sharma, Meha Sharma
  Indian Journal of Endocrinology and Metabolism.2020; 24(5): 434.     CrossRef

Citations

Citations to this article as recorded by  

• Novel pharmacological interventions for diabetic kidney disease
  Seng Kiong Tan, Jairo A. Pinzon-Cortes, Mark E. Cooper
  Current Opinion in Nephrology & Hypertension.2024; 33(1): 13.     CrossRef
• Integrated analysis reveals crosstalk between pyroptosis and immune regulation in renal fibrosis
  Fengxia Bai, Longchao Han, Jifeng Yang, Yuxiu Liu, Xiangmeng Li, Yaqin Wang, Ruijian Jiang, Zhaomu Zeng, Yan Gao, Haisong Zhang
  Frontiers in Immunology.2024;[Epub]     CrossRef
• Di (2-ethylhexyl) phthalate and polystyrene microplastics co-exposure caused oxidative stress to activate NF-κB/NLRP3 pathway aggravated pyroptosis and inflammation in mouse kidney
  Shanshan Li, Xuedie Gu, Muyue Zhang, Qihang Jiang, Tong Xu
  Science of The Total Environment.2024; 926: 171817.     CrossRef
• Fluorofenidone attenuates renal fibrosis by inhibiting lysosomal cathepsin‑mediated NLRP3 inflammasome activation
  Linfeng Zheng, Wenjuan Mei, Jing Zhou, Xin Wei, Zhijuan Huang, Xiaozhen Lin, Li Zhang, Wei Liu, Qian Wu, Jinhong Li, Yan Yan
  Experimental and Therapeutic Medicine.2024;[Epub]     CrossRef
• HIF1α-BNIP3-mediated mitophagy protects against renal fibrosis by decreasing ROS and inhibiting activation of the NLRP3 inflammasome
  Jialin Li, Qisheng Lin, Xinghua Shao, Shu Li, Xuying Zhu, Jingkui Wu, Shan Mou, Leyi Gu, Qin Wang, Minfang Zhang, Kaiqi Zhang, Jiayue Lu, Zhaohui Ni
  Cell Death & Disease.2023;[Epub]     CrossRef
• Pyroptosis in renal inflammation and fibrosis: current knowledge and clinical significance
  Ya Liu, Haibo Lei, Wenyou Zhang, Qichang Xing, Renzhu Liu, Shiwei Wu, Zheng Liu, Qingzi Yan, Wencan Li, Xiang Liu, Yixiang Hu
  Cell Death & Disease.2023;[Epub]     CrossRef
• Tubular injury in diabetic kidney disease: molecular mechanisms and potential therapeutic perspectives
  Yu Wang, Mingyue Jin, Chak Kwong Cheng, Qiang Li
  Frontiers in Endocrinology.2023;[Epub]     CrossRef
• Hederagenin inhibits high glucose‐induced fibrosis in human renal cells by suppression of NLRP3 inflammasome activation through reducing cathepsin B expression
  Guohua Yang, Wang Yang, Hairong Jiang, Qing Yi, Wei Ma
  Chemical Biology & Drug Design.2023; 102(6): 1409.     CrossRef
• Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis
  Rikke Nørregaard, Henricus A. M. Mutsaers, Jørgen Frøkiær, Tae-Hwan Kwon
  Physiological Reviews.2023; 103(4): 2847.     CrossRef
• Adenine model of chronic renal failure in rats to determine whether MCC950, an NLRP3 inflammasome inhibitor, is a renopreventive
  Mahmoud S. Sabra, Fahmy K. Hemida, Essmat A. H. Allam
  BMC Nephrology.2023;[Epub]     CrossRef
• Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome
  Yun Zhang, Song Zhang, Bolin Li, Yingchun Luo, Yongtai Gong, Xuexin Jin, Jiawei Zhang, Yun Zhou, Xiaozhen Zhuo, Zixi Wang, Xinbo Zhao, Xuejie Han, Yunlong Gao, Hui Yu, Desen Liang, Shiqi Zhao, Danghui Sun, Dingyu Wang, Wei Xu, Guangjin Qu, Wanlan Bo, Dan
  Cardiovascular Research.2022; 118(3): 785.     CrossRef
• The NLRP3 inflammasome in fibrosis and aging: The known unknowns
  Yanqing Liu, Xuezeng Xu, Wangrui Lei, Yuxuan Hou, Yan Zhang, Ran Tang, Zhi Yang, Ye Tian, Yanli Zhu, Changyu Wang, Chao Deng, Shaofei Zhang, Yang Yang
  Ageing Research Reviews.2022; 79: 101638.     CrossRef
• Research progress of endothelial‐mesenchymal transition in diabetic kidney disease
  Ying Chen, Hang Zou, Hongwei Lu, Hong Xiang, Shuhua Chen
  Journal of Cellular and Molecular Medicine.2022; 26(12): 3313.     CrossRef
• Exploring the mechanism of Shendi Bushen capsule in anti-renal fibrosis using metabolomics theory and network analysis
  Tianwei Meng, Hong Chang, Hongyu Meng
  Molecular Omics.2022; 18(9): 873.     CrossRef
• Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats
  Wan Seok Kang, Woo Kwon Jung, Su-Bin Park, Hyung Rae Kim, Junghyun Kim
  Biomedicine & Pharmacotherapy.2021; 137: 111297.     CrossRef
• Long‐Term Dipeptidyl Peptidase 4 Inhibition Worsens Hypertension and Renal and Cardiac Abnormalities in Obese Spontaneously Hypertensive Heart Failure Rats
  Edwin K. Jackson, Zaichuan Mi, Delbert G. Gillespie, Dongmei Cheng, Stevan P. Tofovic
  Journal of the American Heart Association.2021;[Epub]     CrossRef
• Disulfiram inhibits inflammation and fibrosis in a rat unilateral ureteral obstruction model by inhibiting gasdermin D cleavage and pyroptosis
  Yu Zhang, Ruicheng Zhang, Xiaohu Han
  Inflammation Research.2021; 70(5): 543.     CrossRef
• Inflammasome as an Effective Platform for Fibrosis Therapy
  Ting-Ting Chen, Feng Xiao, Nan Li, Shan Shan, Meng Qi, Zi-Ying Wang, Sheng-Nan Zhang, Wei Wei, Wu-Yi Sun
  Journal of Inflammation Research.2021; Volume 14: 1575.     CrossRef
• Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?
  Xin Huang, Yimin Khoong, Chengyao Han, Dai Su, Hao Ma, Shuchen Gu, Qingfeng Li, Tao Zan
  Frontiers in Physiology.2021;[Epub]     CrossRef
• Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species
  Tsung-Jui Wu, Yi-Jen Hsieh, Chia-Wen Lu, Chung-Jen Lee, Bang-Gee Hsu
  International Journal of Molecular Sciences.2021; 22(20): 11190.     CrossRef
• Psidium guajava Flavonoids Prevent NLRP3 Inflammasome Activation and Alleviate the Pancreatic Fibrosis in a Chronic Pancreatitis Mouse Model
  Guixian Zhang, Liming Tang, Hongbin Liu, Dawei Liu, Manxue Wang, Jun Cai, Weijun Liu, Wei Nie, Yi Zhang, Xiaomeng Yu
  The American Journal of Chinese Medicine.2021; 49(08): 2001.     CrossRef
• Effect and Regulation of the NLRP3 Inflammasome During Renal Fibrosis
  Hong Zhang, Zhengchao Wang
  Frontiers in Cell and Developmental Biology.2020;[Epub]     CrossRef
• Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway
  Honglian Li, Ruirui Lu, Yu Pang, Jicheng Li, Yiwen Cao, Hongxin Fu, Guoxing Fang, Qiuhe Chen, Bihao Liu, Junbiao Wu, Yuan Zhou, Jiuyao Zhou
  Frontiers in Pharmacology.2020;[Epub]     CrossRef
• Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats
  Rui Yang, Qiang Jia, Yan Li, Shomaila Mehmood
  Experimental Biology and Medicine.2020; 245(14): 1280.     CrossRef

Citations

Citations to this article as recorded by  

• Clinical Significance of PCSK9 and Soluble P-selectin in Predicting Major Adverse Cardiovascular Events After Primary Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome
  Yao Yao, Qining Qiu, Xiaoye Li, Zi Wang, Shikun Xu, Qianzhou Lv
  Cardiovascular Innovations and Applications.2024;[Epub]     CrossRef
• Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing
  Pablo Corral, Carlos A. Aguilar Salinas, María Gabriela Matta, Valeria Zago, Laura Schreier
  Current Atherosclerosis Reports.2023; 25(12): 899.     CrossRef
• Relationship of sortilin and proprotein convertase subtilisin/kexin type 9 in blood serum with the severity of carotid and coronary atherosclerosis in hypertensive patients
  Yu. Yu. Vukolova, I. V. Gubareva
  Russian Journal of Cardiology.2022; 27(2S): 4903.     CrossRef
• PCSK9 Inhibition could be Effective for Acute Myocardial Infarction
  Baris Gencer, François Mach
  Current Medicinal Chemistry.2022; 29(6): 1016.     CrossRef
• Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study
  Lina S. Silva-Bermúdez, Andrea Vargas-Villanueva, Carlos A. Sánchez-Vallejo, Ana C. Palacio, Andrés F. Buitrago, Carlos O. Mendivil
  Lipids in Health and Disease.2022;[Epub]     CrossRef
• Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Inversely Associated with N-Terminal Pro B-Type Natriuretic Peptide in Older Men and Women
  Francesco Spannella, Federico Giulietti, Roberta Galeazzi, Anna Passarelli, Serena Re, Chiara Di Pentima, Massimiliano Allevi, Paolo Magni, Riccardo Sarzani
  Biomedicines.2022; 10(8): 1961.     CrossRef
• Sex difference in circulating PCSK9 and its clinical implications
  Fang Jia, Si-Fan Fei, De-Bing Tong, Cong Xue, Jian-Jun Li
  Frontiers in Pharmacology.2022;[Epub]     CrossRef
• Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall
  Yanan Guo, Binjie Yan, Yu Gui, Zhihan Tang, Shi Tai, Shenghua Zhou, Xi‐Long Zheng
  Journal of Cellular Physiology.2021; 236(4): 2333.     CrossRef
• PCSK9 levels do not predict severity and recurrence of cardiovascular events in patients with acute myocardial infarction
  Marianne Zeller, Gilles Lambert, Michel Farnier, Maud Maza, Brice Nativel, Luc Rochette, Catherine Vergely, Yves Cottin
  Nutrition, Metabolism and Cardiovascular Diseases.2021; 31(3): 880.     CrossRef
• Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction
  Jing Gao, Ya-Nan Yang, Zhuang Cui, Si-Yuan Feng, Jing Ma, Chang-Ping Li, Yin Liu
  Lipids in Health and Disease.2021;[Epub]     CrossRef
• Circulating Biomarkers for Cardiovascular Disease Risk Prediction in Patients With Cardiovascular Disease
  Yuen-Kwun Wong, Hung-Fat Tse
  Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
• Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis
  Jiahui Liu, Fangfang Fan, Xingyu Luo, Wenjun Ji, Yaokun Liu, Yan Zhang, Bo Zheng
  Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
• PCSK9 in acute coronary syndrome: analysis of associations with clinical and laboratory characteristics
  Yu. A. Drenina, K. Yu. Nikolaev
  Cardiovascular Therapy and Prevention.2020; 19(4): 2484.     CrossRef
• Relation of Proprotein Convertase Subtilisin/Kexin Type 9 to Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention
  Ik Jun Choi, Sungmin Lim, Dongjae Lee, Won Jik Lee, Kwan Yong Lee, Mi-Jeong Kim, Doo Soo Jeon
  The American Journal of Cardiology.2020; 133: 54.     CrossRef
• A Narrative Review and Expert Panel Recommendations on Dyslipidaemia Management After Acute Coronary Syndrome in Countries Outside Western Europe and North America
  Ashraf Reda, Wael Almahmeed, Idit Dobrecky-Mery, Po-Hsun Huang, Ursulo Juarez-Herrera, Naresh Ranjith, Tobias Sayre, Miguel Urina-Triana
  Advances in Therapy.2020; 37(5): 1754.     CrossRef
• PCSK9 concentrations in different stages of subclinical atherosclerosis and their relationship with inflammation
  Štefan Tóth, Peter Olexa, Zdenka Hertelyová, Peter Štefanič, Ivan Kopolovets, Peter Berek, Vladimir Filip, Ryan Chakravarty, Monika Široká, Daniel Pella
  Open Chemistry.2020; 18(1): 1011.     CrossRef
• Association of serum proprotein convertase subtilisin/kexin type 9 with early atherosclerosis in newly diagnosed type 2 diabetes mellitus
  Wen Guo, Yingyun Gong, Jie Li, Pei Qin, Jing Lu, Xiaona Li, Wenfang Zhu, Nianzhen Xu, Hongwen Zhou, Qun Zhang
  Nutrition, Metabolism and Cardiovascular Diseases.2019; 29(8): 815.     CrossRef
• PCSK9 and atherosclerosis burden in the coronary arteries of patients undergoing coronary angiography
  Yunes Panahi, Mohsen Sadeghi Ghahrodi, Mohsen Jamshir, Mohammad Amin Safarpour, Vanessa Bianconi, Matteo Pirro, Maryam Moshkani Farahani, Amirhossein Sahebkar
  Clinical Biochemistry.2019; 74: 12.     CrossRef
• Association of PCSK9 plasma levels with metabolic patterns and coronary atherosclerosis in patients with stable angina
  Chiara Caselli, Serena Del Turco, Rosetta Ragusa, Valentina Lorenzoni, Michiel De Graaf, Giuseppina Basta, Arthur Scholte, Raffaele De Caterina, Danilo Neglia
  Cardiovascular Diabetology.2019;[Epub]     CrossRef
• PCSK9 inhibition and inflammation: A narrative review
  Massimiliano Ruscica, Lale Tokgözoğlu, Alberto Corsini, Cesare R. Sirtori
  Atherosclerosis.2019; 288: 146.     CrossRef
• Letter: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
  Jin Hwa Kim
  Diabetes & Metabolism Journal.2018; 42(4): 348.     CrossRef
• Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
  Sung Woo Kim, Keun-Gyu Park
  Diabetes & Metabolism Journal.2018; 42(4): 350.     CrossRef
• Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population
  Gaojun Cai, Lei Yu, Zhiying Huang, Li Li, Xingli Fu
  Lipids in Health and Disease.2018;[Epub]     CrossRef