Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats.

作者: Li Sun , Quan Yuan , Tianhua Xu , Li Yao , Jiangmin Feng

DOI: 10.3389/FPHAR.2017.00545

关键词: Renal functionPioglitazoneFibrosisChemistryRenal fibrosisEndocrinologyMFN2Internal medicineMitochondrionKidneyReceptor

摘要: Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved renoprotection pioglitazone not fully revealed. In present study, renoprotective was investigated 5/6 nephrectomized (Nx) rats TGF-β1-exposed HK-2 cells. attenuated renal injury improved function, as examined by 24 h urinary protein, blood urea nitrogen plasma creatinine Nx rats. Renal fibrosis enhanced expressions profibrotic proteins TGF-β1, fibronectin collagen I caused were significantly alleviated pioglitazone. addition, protected mitochondrial functions stabilizing membrane potential, inhibiting ROS generation, maintaining ATP production activities complexes III, preventing cytochrome C leakage from mitochondria. also upregulated expression levels synthase β, COX NDUFB8, which downregulated Furthermore, increased fusion Opa-1 Mfn2 decreased fission protein Drp1 expression. The results imply that may exert effects through modulating electron transport chain dynamics CKD. Finally, these recoveries completely or partly inhibited GW9662, suggests at least PPARγ dependent. This study provides evidence for pharmacological treatment

参考文章(38)
J. Dudka, A. Korolczuk, G. Czechowska, M. Maciejewski, I. Widelska, A. Smolen, The role of peroxisome-proliferator-activating receptor gamma agonists: rosiglitazone and 15-deoxy-delta12,14-prostaglandin J2 in chronic experimental cyclosporine A-induced nephrotoxicity. Journal of Physiology and Pharmacology. ,vol. 65, pp. 867- 876 ,(2014)
Donald D Newmeyer, Shelagh Ferguson-Miller, Mitochondria: Releasing power for life and unleashing the machineries of death Cell. ,vol. 112, pp. 481- 490 ,(2003) , 10.1016/S0092-8674(03)00116-8
Chunhua Zhu, Songming Huang, Yanggang Yuan, Guixia Ding, Ronghua Chen, Bicheng Liu, Tianxin Yang, Aihua Zhang, Mitochondrial Dysfunction Mediates Aldosterone-Induced Podocyte Damage: A Therapeutic Target of PPARγ American Journal of Pathology. ,vol. 178, pp. 2020- 2031 ,(2011) , 10.1016/J.AJPATH.2011.01.029
WANSHENG WANG, VIJAY KOKA, HUI Y LAN, Transforming growth factor-beta and Smad signalling in kidney diseases. Nephrology. ,vol. 10, pp. 48- 56 ,(2005) , 10.1111/J.1440-1797.2005.00334.X
E.M.V. de Cavanagh, F. Inserra, M. Ferder, L. Ferder, From Mitochondria to Disease: Role of the Renin-Angiotensin System American Journal of Nephrology. ,vol. 27, pp. 545- 553 ,(2007) , 10.1159/000107757
Stephen L. Archer, Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. The New England Journal of Medicine. ,vol. 369, pp. 2236- 2251 ,(2013) , 10.1056/NEJMRA1215233
Cong Zou, Honglin Hu, Xiaoqing Xi, Zimin Shi, Gongxian Wang, Xueming Huang, Pioglitazone protects against renal ischemia-reperfusion injury by enhancing antioxidant capacity Journal of Surgical Research. ,vol. 184, pp. 1092- 1095 ,(2013) , 10.1016/J.JSS.2013.03.027
Juan M. Zolezzi, Carmen Silva-Alvarez, Daniela Ordenes, Juan A. Godoy, Francisco J. Carvajal, Manuel J. Santos, Nibaldo C. Inestrosa, Peroxisome Proliferator-Activated Receptor (PPAR) γ and PPARα Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders? PLoS ONE. ,vol. 8, pp. e64019- ,(2013) , 10.1371/JOURNAL.PONE.0064019
Peter Ochodnicky, Lucia Mesarosova, Hana Cernecka, Jan Klimas, Peter Krenek, Maaike Goris, Richard P.E. van Dokkum, Robert H. Henning, Jan Kyselovic, Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat European Journal of Pharmacology. ,vol. 730, pp. 51- 60 ,(2014) , 10.1016/J.EJPHAR.2014.02.023