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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
  • 5,720 View
  • 132 Download
  • 24 Web of Science
  • 24 Crossref
AbstractAbstract 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.

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  
  • 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
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
  • 4,505 View
  • 51 Download
  • 2 Web of Science
AbstractAbstract PDFSupplementary MaterialPubReader   

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
  • 5,328 View
  • 58 Download
  • 26 Web of Science
  • 24 Crossref
AbstractAbstract PDFPubReader   
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

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
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    Mieczysław Dutka, Karolina Zimmer, Michał Ćwiertnia, Tomasz Ilczak, Rafał Bobiński
    Heart Failure Reviews.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
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    Frontiers in Pharmacology.2022;[Epub]     CrossRef
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    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
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    Nutrition, Metabolism and Cardiovascular Diseases.2021; 31(3): 880.     CrossRef
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    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
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    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
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    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
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    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

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