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Yun-A Jung  (Jung YA) 2 Articles
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
  • 5,956 View
  • 99 Download
  • 10 Web of Science
  • 10 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   

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 to this article as recorded by  
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    British Journal of Pharmacology.2023; 180(22): 2846.     CrossRef
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    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
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
  • 5,746 View
  • 132 Download
  • 24 Web of Science
  • 24 Crossref
AbstractAbstract PDFPubReader   

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.


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.


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.


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 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
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  • The NLRP3 inflammasome in fibrosis and aging: The known unknowns
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    Ageing Research Reviews.2022; 79: 101638.     CrossRef
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  • Long‐Term Dipeptidyl Peptidase 4 Inhibition Worsens Hypertension and Renal and Cardiac Abnormalities in Obese Spontaneously Hypertensive Heart Failure Rats
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    Xin Huang, Yimin Khoong, Chengyao Han, Dai Su, Hao Ma, Shuchen Gu, Qingfeng Li, Tao Zan
    Frontiers in Physiology.2021;[Epub]     CrossRef
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