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Yun-A Jung  (Jung YA) 1 Article
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
DOI: https://doi.org/10.3803/EnM.2017.32.1.115
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  • 72 Download
  • 14 Citations
AbstractAbstract PDFPubReader   
Background

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.

Methods

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.

Results

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.

Conclusion

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

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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