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Endocrinol Metab : Endocrinology and Metabolism


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Kwi-Hyun Bae  (Bae KH) 2 Articles
Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
Kwi-Hyun Bae, Jung Beom Seo, Yun-A Jung, Hye-Young Seo, Sun Hee Kang, Hui-Jeon Jeon, Jae Man Lee, Sungwoo Lee, Jung-Guk Kim, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
Endocrinol Metab. 2017;32(1):115-123.   Published online February 28, 2017
  • 4,632 View
  • 75 Download
  • 13 Web of Science
  • 14 Crossref
AbstractAbstract PDFPubReader   

Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice.


We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study.


Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway.


The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.


Citations to this article as recorded by  
  • The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis
    Shiyan Jian, Kang Yang, Lingna Zhang, Limeng Zhang, Zhongquan Xin, Chaoyu Wen, Shansong He, Jinping Deng, Baichuan Deng
    Food Frontiers.2023; 4(1): 262.     CrossRef
  • Druggability of lipid metabolism modulation against renal fibrosis
    Yuan-yuan Chen, Xiao-guang Chen, Sen Zhang
    Acta Pharmacologica Sinica.2022; 43(3): 505.     CrossRef
  • Lobeglitazone attenuates fibrosis in corneal fibroblasts by interrupting TGF-beta-mediated Smad signaling
    Selikem Nuwormegbe, Na-Young Park, Sun Woong Kim
    Graefe's Archive for Clinical and Experimental Ophthalmology.2022; 260(1): 149.     CrossRef
  • Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
    Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
    Diabetes Therapy.2021; 12(1): 171.     CrossRef
  • Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
    Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
    Diabetes & Metabolism Journal.2021; 45(3): 326.     CrossRef
  • Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway
    Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim
    Endocrinology and Metabolism.2021; 36(5): 1095.     CrossRef
  • Protocol for a preclinical systematic review and meta-analysis of pharmacological targeting of peroxisome proliferator-activated receptors in experimental renal injury
    William P Martin, Yeong H D Chuah, Emer Conroy, Alison L Reynolds, Conor Judge, Francisco J López-Hernández, Carel W le Roux, Neil G Docherty
    BMJ Open Science.2021;[Epub]     CrossRef
  • Stevioside inhibits unilateral ureteral obstruction‐induced kidney fibrosis and upregulates renal PPARγ expression in mice
    Wei Shen, Ke Fan, Ying Zhao, Junyan Zhang, Meilin Xie
    Journal of Food Biochemistry.2020;[Epub]     CrossRef
  • FBW7 Regulates the Autophagy Signal in Mesangial Cells Induced by High Glucose
    Chenlin Gao, Fang Fan, Jiao Chen, Yang Long, Shi Tang, Chunxia Jiang, Yong Xu
    BioMed Research International.2019; 2019: 1.     CrossRef
  • Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice
    Sorim Choung, Kyong Hye Joung, Bo Ram You, Sang Ki Park, Hyun Jin Kim, Bon Jeong Ku
    PPAR Research.2018; 2018: 1.     CrossRef
  • VCE‐004.3, a cannabidiol aminoquinone derivative, prevents bleomycin‐induced skin fibrosis and inflammation through PPARγ‐ and CB2 receptor‐dependent pathways
    Carmen del Rio, Irene Cantarero, Belén Palomares, María Gómez‐Cañas, Javier Fernández‐Ruiz, Carolina Pavicic, Adela García‐Martín, Maria Luz Bellido, Rafaela Ortega‐Castro, Carlos Pérez‐Sánchez, Chary López‐Pedrera, Giovanni Appendino, Marco A Calzado, Ed
    British Journal of Pharmacology.2018; 175(19): 3813.     CrossRef
  • EHP-101, an oral formulation of the cannabidiol aminoquinone VCE-004.8, alleviates bleomycin-induced skin and lung fibrosis
    Adela García-Martín, Martín Garrido-Rodríguez, Carmen Navarrete, Carmen del Río, María L. Bellido, Giovanni Appendino, Marco A. Calzado, Eduardo Muñoz
    Biochemical Pharmacology.2018; 157: 304.     CrossRef
  • Effects of Lobeglitazone, a New Thiazolidinedione, on Osteoblastogenesis and Bone Mineral Density in Mice
    Kyoung Min Kim, Hyun-Jin Jin, Seo Yeon Lee, Hyo Jin Maeng, Gha Young Lee, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang, Soo Lim
    Endocrinology and Metabolism.2017; 32(3): 389.     CrossRef
  • Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks
    Soo Lim, Kyoung Min Kim, Sin Gon Kim, Doo Man Kim, Jeong-Taek Woo, Choon Hee Chung, Kyung Soo Ko, Jeong Hyun Park, Yongsoo Park, Sang Jin Kim, Hak Chul Jang, Dong Seop Choi
    Diabetes & Metabolism Journal.2017; 41(5): 377.     CrossRef
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Obesity and Metabolism
Transcriptional Regulation of Fibroblast Growth Factor 21 Expression
Kwi-Hyun Bae, Jung-Guk Kim, Keun-Gyu Park
Endocrinol Metab. 2014;29(2):105-111.   Published online June 26, 2014
  • 4,199 View
  • 59 Download
  • 25 Web of Science
  • 23 Crossref
AbstractAbstract PDFPubReader   

Fibroblast growth factor 21 (FGF21) is an attractive target for treating metabolic disease due to its wide-ranging beneficial effects on glucose and lipid metabolism. Circulating FGF21 levels are increased in insulin-resistant states; however, endogenous FGF21 fails to improve glucose and lipid metabolism in obesity, suggesting that metabolic syndrome is an FGF21-resistant state. Therefore, transcription factors for FGF21 are potential drug targets that could increase FGF21 expression in obesity and reduce FGF21 resistance. Despite many studies on the metabolic effects of FGF21, the transcriptional regulation of FGF21 gene expression remains controversial and is not fully understood. As the FGF21 transcription factor pathway is one of the most promising targets for the treatment of metabolic syndrome, further investigation of FGF21 transcriptional regulation is required.


Citations to this article as recorded by  
  • Relationship between FGF21 and drug or nondrug therapy of type 2 diabetes mellitus
    Chang Guo, Li Zhao, Yanyan Li, Xia Deng, Guoyue Yuan
    Journal of Cellular Physiology.2021; 236(1): 55.     CrossRef
  • Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome
    Pirkka T. Pekkarinen, Markus B. Skrifvars, Ville Lievonen, Pekka Jakkula, Laura Albrecht, Pekka Loisa, Marjaana Tiainen, Ville Pettilä, Matti Reinikainen, Johanna Hästbacka
    Scientific Reports.2021;[Epub]     CrossRef
  • Epigenetic Regulation of Processes Related to High Level of Fibroblast Growth Factor 21 in Obese Subjects
    Teresa Płatek, Anna Polus, Joanna Góralska, Urszula Raźny, Agnieszka Dziewońska, Agnieszka Micek, Aldona Dembińska-Kieć, Bogdan Solnica, Małgorzata Malczewska-Malec
    Genes.2021; 12(2): 307.     CrossRef
  • Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine
    Han Fang, Kirsten P. Stone, Laura A. Forney, Desiree Wanders, Thomas W. Gettys
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
  • The Presence of Urinary Ketones according to Metabolic Status and Obesity
    Bo-Reum Kim, Jeong Woo Seo, Sang Man Kim, Kyu-Nam Kim, Nam-Seok Joo
    Journal of Korean Medical Science.2020;[Epub]     CrossRef
  • MS-275 induces hepatic FGF21 expression via H3K18ac-mediated CREBH signal
    Qi Zhang, Qin Zhu, Ruyuan Deng, Feiye Zhou, Linlin Zhang, Shushu Wang, Kecheng Zhu, Xiao Wang, Libin Zhou, Qing Su
    Journal of Molecular Endocrinology.2019; 62(4): 187.     CrossRef
  • Spontaneous ketonuria and risk of incident diabetes: a 12 year prospective study
    Gyuri Kim, Sang-Guk Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Ele Ferrannini, Yong-ho Lee, Nam H. Cho
    Diabetologia.2019; 62(5): 779.     CrossRef
  • Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges
    Úrsula Martínez-Garza, Daniel Torres-Oteros, Alex Yarritu-Gallego, Pedro F. Marrero, Diego Haro, Joana Relat
    International Journal of Molecular Sciences.2019; 20(19): 4692.     CrossRef
  • Berberine-induced activation of AMPK increases hepatic FGF21 expression via NUR77
    Feiye Zhou, Mengyao Bai, Yuqing Zhang, Qin Zhu, Linlin Zhang, Qi Zhang, Shushu Wang, Kecheng Zhu, Yun Liu, Xiao Wang, Libin Zhou
    Biochemical and Biophysical Research Communications.2018; 495(2): 1936.     CrossRef
  • Practical prospects for boosting hepatic production of the “pro-longevity” hormone FGF21
    Mark F. McCarty
    Hormone Molecular Biology and Clinical Investigation.2017;[Epub]     CrossRef
  • The regulation of FGF21 gene expression by metabolic factors and nutrients
    Anjeza Erickson, Régis Moreau
    Hormone Molecular Biology and Clinical Investigation.2017;[Epub]     CrossRef
  • Diabetes Mellitus and Sepsis
    Silvia C. Trevelin, Daniela Carlos, Matteo Beretta, João S. da Silva, Fernando Q. Cunha
    Shock.2017; 47(3): 276.     CrossRef
  • The U-shaped relationship between fibroblast growth factor 21 and microvascular complication in type 2 diabetes mellitus
    Chan-Hee Jung, Sang-Hee Jung, Bo-Yeon Kim, Chul-Hee Kim, Sung-Koo Kang, Ji-Oh Mok
    Journal of Diabetes and its Complications.2017; 31(1): 134.     CrossRef
  • Fibroblast Growth Factor 21—Metabolic Role in Mice and Men
    Harald Staiger, Michaela Keuper, Lucia Berti, Martin Hrabě de Angelis, Hans-Ulrich Häring
    Endocrine Reviews.2017; 38(5): 468.     CrossRef
  • Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21
    Jay W Porter, Joe L Rowles, Justin A Fletcher, Terese M Zidon, Nathan C Winn, Leighton T McCabe, Young-Min Park, James W Perfield, John P Thyfault, R Scott Rector, Jaume Padilla, Victoria J Vieira-Potter
    Journal of Endocrinology.2017; 235(2): 97.     CrossRef
  • Hepatic Fgf21 Expression Is Repressed after Simvastatin Treatment in Mice
    Panos Ziros, Zoi Zagoriti, George Lagoumintzis, Venetsana Kyriazopoulou, Ralitsa P. Iskrenova, Evagelia I. Habeos, Gerasimos P. Sykiotis, Dionysios V. Chartoumpekis, Ioannis G Habeos, Kostas Pantopoulos
    PLOS ONE.2016; 11(9): e0162024.     CrossRef
  • Association between insulin resistance and impairment of FGF21 signal transduction in skeletal muscles
    Ja Young Jeon, Sung-E Choi, Eun Suk Ha, Tae Ho Kim, Jong Gab Jung, Seung Jin Han, Hae Jin Kim, Dae Jung Kim, Yup Kang, Kwan-Woo Lee
    Endocrine.2016; 53(1): 97.     CrossRef
  • Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury
    Yanlong Liu, Cuiqing Zhao, Jian Xiao, Liming Liu, Min Zhang, Cuiling Wang, Guicheng Wu, Ming-Hua Zheng, Lan-Man Xu, Yong-Ping Chen, Moosa Mohammadi, Shao-Yu Chen, Matthew Cave, Craig McClain, Xiaokun Li, Wenke Feng
    Scientific Reports.2016;[Epub]     CrossRef
  • The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis
    Kyung Mook Choi
    Endocrinology and Metabolism.2016; 31(1): 1.     CrossRef
  • Physiological and Pharmacological Roles of FGF21 in Cardiovascular Diseases
    Peng Cheng, Fangfang Zhang, Lechu Yu, Xiufei Lin, Luqing He, Xiaokun Li, Xuemian Lu, Xiaoqing Yan, Yi Tan, Chi Zhang
    Journal of Diabetes Research.2016; 2016: 1.     CrossRef
  • Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases
    Fangfang Zhang, Lechu Yu, Xiufei Lin, Peng Cheng, Luqing He, Xiaokun Li, Xuemian Lu, Yi Tan, Hong Yang, Lu Cai, Chi Zhang
    Molecular Endocrinology.2015; 29(10): 1400.     CrossRef
  • AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells
    Jinmi Lee, Seok-Woo Hong, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
    Molecular and Cellular Endocrinology.2015; 414: 148.     CrossRef
  • Articles in 'Endocrinology and Metabolism' in 2014
    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
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