- Drug/Regimen
- Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
-
Mi-Jin Kim, Na-young Kim, Yun-A Jung, Seunghyeong Lee, Gwon-Soo Jung, Jung-Guk Kim, In-Kyu Lee, Sungwoo Lee, Yeon-Kyung Choi, Keun-Gyu Park
-
Diabetes Metab J. 2020;44(1):186-192. Published online October 31, 2019
-
DOI: https://doi.org/10.4093/dmj.2018.0271
-
-
6,349
View
-
112
Download
-
10
Web of Science
-
10
Crossref
-
 Abstract
 PDF Supplementary Material PubReader
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 
- Complications
- Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome
-
Jung Beom Seo, Yeon-Kyung Choi, Hye-In Woo, Yun-A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
-
Diabetes Metab J. 2019;43(6):830-839. Published online March 5, 2019
-
DOI: https://doi.org/10.4093/dmj.2018.0181
-
-
6,044
View
-
135
Download
-
27
Web of Science
-
28
Crossref
-
Abstract
PDFPubReader
- Background
The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis. MethodsWe examined the effects of gemigliptin on renal tubulointerstitial fibrosis induced in mice by unilateral ureteral obstruction (UUO). Using immunohistochemical and Western blot analysis, we quantitated components of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment, and in vitro in human kidney tubular epithelial human renal proximal tubule cells (HK-2) cells, we further analyzed the effect of gemigliptin on transforming growth factor-β (TGF-β)-stimulated production of profibrotic proteins. ResultsImmunohistological examination revealed that gemigliptin ameliorated UUO-induced tubular atrophy and renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1β, which had all been markedly increased by UUO. In line with the in vivo results, TGF-β markedly increased NLRP3 inflammasome markers, which were attenuated by gemigliptin treatment. Furthermore, gemigliptin treatment attenuated phosphorylated nuclear factor-κB levels, which had been increased in the UUO kidney as well as in TGF-β-treated cultured renal cells. ConclusionThe present study shows that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis and the renoprotective effect of gemigliptin is associated with attenuation of NLRP3 inflammasome activation.
-
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 - Gemigliptin mitigates TGF-β-induced renal fibrosis through FGF21-mediated inhibition of the TGF-β/Smad3 signaling pathway
Jun-Kyu Byun, Gwon-Soo Jung
Biochemical and Biophysical Research Communications.2024; 733: 150425. CrossRef - Uncovering the Role of Anoikis-Related Genes in Modulating Immune Infiltration and Pathogenesis of Diabetic Kidney Disease
Jiaqiong Lin, Yan Lin, Xiaoyong Li, Fei He, Qinyuan Gao, Yuanjun Wang, Zena Huang, Fu Xiong
Journal of Inflammation Research.2024; Volume 17: 4975. CrossRef - Activation of NLRP3 inflammasome in patients with renal transplantation: relation to allograft dysfunction, inflammation, and renal fibrosis
Hayam Abdel Meguid El Aggan, Hala Saddik El-Wakil, Sabah Abdel-Hady Mahmoud, Aya Ahmad Saad
Alexandria Journal of Medicine.2024; 60(1): 249. CrossRef - Therapy Targeted to the NLRP3 Inflammasome in Chronic Kidney Disease
Yong Ji, Hu Hua, Zhanjun Jia, Aihua Zhang, Guixia Ding
Kidney Diseases.2024; : 369. 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
|
KDA
