Peroxisome proliferator-activated receptor-γ agonist pioglitazone fails to attenuate renal fibrosis caused by unilateral ureteral obstruction in mice

Summary

Renal tubulointerstitial fibrosis is the common ending of progreβsive renal disease. It is worth developing new ways to stop the progreβs of renal fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for a-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4+ T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.

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Correspondence to Gang Xu 徐 钢.

Additional information

This project was financially supported by grants from the National Natural Science Foundation of China (No. 81470948, No. 81270770, and No. 81300575), and Hubei Provincial Health and Family Planning Youth Project of China (No. WJ2015Q007).

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Zhang, Y., Wang, J., Zhou, Q. et al. Peroxisome proliferator-activated receptor-γ agonist pioglitazone fails to attenuate renal fibrosis caused by unilateral ureteral obstruction in mice. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 41–47 (2016). https://doi.org/10.1007/s11596-016-1539-1

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Key words

  • renal fibrosis
  • unilateral ureteral obstruction
  • PPAR-γ
  • T lymphocyte