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Sun L, Yuan Q, Xu T, et al. Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats. Front Pharmacol. 2017;8:545doi: 10.3389/fphar.2017.00545.
Sun, L., Yuan, Q., Xu, T., Yao, L., Feng, J., Ma, J., Wang, L., Lu, C., & Wang, D. (2017). Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats. Frontiers in pharmacology, 8545. https://doi.org/10.3389/fphar.2017.00545
Sun, Li, et al. "Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats." Frontiers in pharmacology vol. 8 (2017): 545. doi: https://doi.org/10.3389/fphar.2017.00545
Sun L, Yuan Q, Xu T, Yao L, Feng J, Ma J, Wang L, Lu C, Wang D. Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats. Front Pharmacol. 2017 Aug 15;8:545. doi: 10.3389/fphar.2017.00545. eCollection 2017. PMID: 28860994; PMCID: PMC5559534.
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Front Pharmacol. 2017 Aug 15;8:545. doi: 10.3389/fphar.2017.00545. eCollection 2017.

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

Frontiers in pharmacology

Li Sun, Quan Yuan, Tianhua Xu, Li Yao, Jiangmin Feng, Jianfei Ma, Lining Wang, Changlong Lu, Danan Wang

Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of China Medical UniversityShenyang, China.
  2. Department of Orthopedic Surgery, Shengjing Hospital of China Medical UniversityShenyang, China.
  3. Department of Immunology, China Medical UniversityShenyang, China.

PMID: 28860994 PMCID: PMC5559534 DOI: 10.3389/fphar.2017.00545

Abstract

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

Keywords: chronic kidney diseases; fibrosis; mitochondrial dysfunction; peroxisome proliferator-activated receptor γ; pioglitazone

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