title: Peroxisome proliferator-activated receptor-γ agonist pioglitazone fails to attenuate renal fibrosis caused by unilateral ureteral obstruction in mice.
abstract: 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. 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.
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qiao-Dan
authors.initials: QD
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Cong-Hui
authors.initials: CH
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. xugang@tjh.tjmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014524:Urethral Obstruction / Q000150:complications*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D047495:PPAR gamma; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077205:Pioglitazone
keywords: PPAR-γ; T lymphocyte; renal fibrosis; unilateral ureteral obstruction
references.citation: Transplantation. 1999 Jun 27;67(12):1548-55
references.pmid: 10401761
references.citation: Am J Nephrol. 2012;36(4):386-96
references.pmid: 23052013
references.citation: Horm Metab Res. 2014 Apr;46(4):240-4
references.pmid: 24136780
references.citation: Cancer Immunol Immunother. 2013 Feb;62(2):225-36
references.pmid: 22864396
references.citation: Eur J Pharmacol. 2014 May 5;730:51-60
references.pmid: 24582928
references.citation: J Am Soc Nephrol. 2015 Dec;26(12 ):2896-8
references.pmid: 26032812
references.citation: J Surg Res. 2012 Nov;178(1):460-5
references.pmid: 22507688
references.citation: Transl Res. 2015 Oct;166(4):375-83
references.pmid: 26001596
references.citation: Am J Physiol Renal Physiol. 2010 May;298(5):F1263-75
references.pmid: 20015942
references.citation: J Am Soc Nephrol. 1998 Jun;9(6):1008-17
references.pmid: 9621283
references.citation: Horm Metab Res. 2012 Nov;44(12):914-8
references.pmid: 22723267
references.citation: J Am Soc Nephrol. 2009 Nov;20(11):2380-8
references.pmid: 19797472
references.citation: Nature. 2012 Jun 28;486(7404):549-53
references.pmid: 22722857
references.citation: Cell Biosci. 2015 Jan 27;5:5
references.pmid: 25973172
references.citation: Inflamm Bowel Dis. 2005 Mar;11(3):244-52
references.pmid: 15735430
references.citation: J Korean Med Sci. 2010 Jan;25(1):35-41
references.pmid: 20052345
references.citation: Scand J Clin Lab Invest. 2012 May;72(3):221-9
references.pmid: 22276947
references.citation: West Indian Med J. 2014 Jan;63(1):20-5
references.pmid: 25303188
references.citation: Trends Endocrinol Metab. 2012 May;23(5):205-15
references.pmid: 22513163
references.citation: J Am Coll Cardiol. 2008 Sep 2;52(10):869-81
references.pmid: 18755353
references.citation: Eur Respir J. 2014 Feb;43(2):409-20
references.pmid: 23794466
references.citation: Int Immunopharmacol. 2011 Dec;11(12):2033-8
references.pmid: 21911083
references.citation: J Appl Toxicol. 2014 Jan;34(1):25-32
references.pmid: 22987311
references.citation: Nephrology (Carlton). 2010 Apr;15(3):327-35
references.pmid: 20470302
references.citation: J Immunol. 2002 Jul 15;169(2):929-36
references.pmid: 12097398
references.citation: Kidney Int. 2010 Aug;78(4):351-62
references.pmid: 20555323
references.citation: J Am Soc Nephrol. 2008 Jan;19(1):182-7
references.pmid: 18057215
references.citation: J Am Soc Nephrol. 2011 May;22(5):802-9
references.pmid: 21474561
references.citation: J Am Soc Nephrol. 2010 Nov;21(11):1819-34
references.pmid: 20864689
references.citation: J Am Soc Nephrol. 2006 Jan;17 (1):17-25
references.pmid: 16291837
references.citation: Int Arch Allergy Immunol. 2003 Oct;132(2):168-76
references.pmid: 14600429
references.citation: Cell Immunol. 2014 May-Jun;289(1-2):106-11
references.pmid: 24754976
references.citation: Eur Heart J. 2006 Jul;27(13):1605-9
references.pmid: 16762982
references.citation: Kidney Int. 2005 Jul;68(1):285-92
references.pmid: 15954919
references.citation: Int J Clin Exp Med. 2015 Apr 15;8(4):5388-96
references.pmid: 26131115