Peroxisome Proliferator-activated Receptor-γ Agonist Pioglitazone Fails to Attenuate Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2016-02, Vol.36 (1), p.41-47
• Main Author: 张颖 王瑾 周巧丹 章从惠 李青 黄帅 詹娟 王堃 刘颜颜 徐钢
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CCL2 - metabolism; Fibrosis; Kidney - pathology; Kidney Diseases - drug therapy; Kidney Diseases - etiology; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; PPAR gamma - agonists; T-Lymphocyte Subsets - drug effects; Thiazolidinediones - administration & dosage; Thiazolidinediones - pharmacology; Thiazolidinediones - therapeutic use; Transforming Growth Factor beta - metabolism; Urethral Obstruction - complications; 临床; 医学; 症状; 诊断
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-016-1539-1

Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress 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. PPARγ agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14 th 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 α-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.