title: Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice.
abstract: BACKGROUND
  Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice.
  
  
  METHODS
  We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study.
  
  
  RESULTS
  Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway.
  
  
  CONCLUSIONS
  The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.|Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Kwi Hyun
authors.identifier: http://orcid.org/0000-0002-0482-2904
authors.initials: KH
authors.lastname: Bae
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jung Beom
authors.initials: JB
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Yun A
authors.initials: YA
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Seo
authors.affiliation: Department of Surgery, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Hui Jeon
authors.initials: HJ
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jae Man
authors.initials: JM
authors.lastname: Lee
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jung Guk
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.|Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea. mine9240@naver.com.
authors.forename: Gwon Soo
authors.initials: GS
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.|Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea. kpark@knu.ac.kr.
authors.forename: Keun Gyu
authors.identifier: http://orcid.org/0000-0002-8403-1298
authors.initials: KG
authors.lastname: Park
keywords: Lobeglitazone; Renal tubulointerstitial fibrosis; Transforming growth factor beta; Unilateral ureteral obstruction