Diabetes & Metabolism Journal

Jung Beom Seo (Seo JB)

3 Articles

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

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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.

Methods

We 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.

Results

Immunohistological 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.

Conclusion

The 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

TLR4 Inhibitor TAK‐242 Protected Henoch–Schonlein Purpura Nephritis in Rats by Regulating Inflammatory Response and Immune Competence via NF‐ κB/NLRP3 Signalling
Yirong Liu, Qiong Wu, Zhenxing Huang, Dongmei Zhou, Chao Cai, Wenliang Luo, Ping Feng
Clinical and Experimental Pharmacology and Physiology.2025;[Epub] CrossRef
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; 10(5): 369. CrossRef
Evaluation of the Effect of an α-Adrenergic Blocker, a PPAR-γ Receptor Agonist, and a Glycemic Regulator on Chronic Kidney Disease in Diabetic Rats
Jorge Morones, Mariana Pérez, Martín Muñoz, Esperanza Sánchez, Manuel Ávila, Jorge Topete, Javier Ventura, Sandra Martínez
International Journal of Molecular Sciences.2024; 25(21): 11372. CrossRef
Regulated cell death in chronic kidney disease: current evidence and future clinical perspectives
Kurt T. K. Giuliani, Benjamin C. Adams, Helen G. Healy, Andrew J. Kassianos
Frontiers in Cell and Developmental Biology.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
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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
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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
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Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats
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Epidemiology
Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes: Sung Woo Kim, Jae-Han Jeon, Jun Sung Moon, Eon Ju Jeon, Mi-Kyung Kim, In-Kyu Lee, Jung Beom Seo, Keun-Gyu Park; Diabetes Metab J. 2019;43(5):718-726. Published online March 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0222

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Abstract PDF Supplementary Material PubReader: Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

Complications
Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome: Kwi-Hyun Bae, Sung Woo Kim, Yeon-Kyung Choi, Jung Beom Seo, Namkyun Kim, Chang-Yeon Kim, Won Kee Lee, Sungwoo Lee, Jung Guk Kim, In-Kyu Lee, Jang Hoon Lee, Keun-Gyu Park; Diabetes Metab J. 2018;42(3):207-214. Published online May 2, 2018; DOI: https://doi.org/10.4093/dmj.2017.0081

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28 Crossref

Abstract PDF PubReader

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.

Methods

From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.

Results

Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.

Conclusion

Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

Citations

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Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
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