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2 "Seunghyeong Lee"
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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
  • 5,679 View
  • 97 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

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
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  • 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
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    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
Original Article
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
  • 5,439 View
  • 128 Download
  • 23 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
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    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
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    Experimental and Therapeutic Medicine.2024;[Epub]     CrossRef
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    Cell Death & Disease.2023;[Epub]     CrossRef
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    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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    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
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Diabetes Metab J : Diabetes & Metabolism Journal