Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
BackgroundRenal 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 dire...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Academya Publishing Co.
2017-02-01
|
Series: | Endocrinology and Metabolism |
Subjects: | |
Online Access: | https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-32-115.pdf |
id |
doaj-de09a9756bc64e98a433a255e49175a2 |
---|---|
record_format |
Article |
spelling |
doaj-de09a9756bc64e98a433a255e49175a22020-11-24T23:15:52ZengAcademya Publishing Co.Endocrinology and Metabolism2093-596X2093-59782017-02-0132111512310.3803/EnM.2017.32.1.115Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in MiceKwi-Hyun Bae0Jung Beom Seo1Yun-A Jung2Hye-Young Seo3Sun Hee Kang4Hui-Jeon Jeon5Jae Man Lee6Sungwoo Lee7Jung-Guk Kim8In-Kyu Lee9Gwon-Soo Jung10Keun-Gyu Park11Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.Department of Surgery, Keimyung 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.Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Korea.New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.BackgroundRenal 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.MethodsWe 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.ResultsThrough 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.ConclusionThe 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.https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-32-115.pdfRenal tubulointerstitial fibrosisLobeglitazoneTransforming growth factor betaUnilateral ureteral obstruction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kwi-Hyun Bae Jung Beom Seo Yun-A Jung Hye-Young Seo Sun Hee Kang Hui-Jeon Jeon Jae Man Lee Sungwoo Lee Jung-Guk Kim In-Kyu Lee Gwon-Soo Jung Keun-Gyu Park |
spellingShingle |
Kwi-Hyun Bae Jung Beom Seo Yun-A Jung Hye-Young Seo Sun Hee Kang Hui-Jeon Jeon Jae Man Lee Sungwoo Lee Jung-Guk Kim In-Kyu Lee Gwon-Soo Jung Keun-Gyu Park Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice Endocrinology and Metabolism Renal tubulointerstitial fibrosis Lobeglitazone Transforming growth factor beta Unilateral ureteral obstruction |
author_facet |
Kwi-Hyun Bae Jung Beom Seo Yun-A Jung Hye-Young Seo Sun Hee Kang Hui-Jeon Jeon Jae Man Lee Sungwoo Lee Jung-Guk Kim In-Kyu Lee Gwon-Soo Jung Keun-Gyu Park |
author_sort |
Kwi-Hyun Bae |
title |
Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice |
title_short |
Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice |
title_full |
Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice |
title_fullStr |
Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice |
title_full_unstemmed |
Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice |
title_sort |
lobeglitazone, a novel peroxisome proliferator-activated receptor γ agonist, attenuates renal fibrosis caused by unilateral ureteral obstruction in mice |
publisher |
Academya Publishing Co. |
series |
Endocrinology and Metabolism |
issn |
2093-596X 2093-5978 |
publishDate |
2017-02-01 |
description |
BackgroundRenal 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.MethodsWe 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.ResultsThrough 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.ConclusionThe 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. |
topic |
Renal tubulointerstitial fibrosis Lobeglitazone Transforming growth factor beta Unilateral ureteral obstruction |
url |
https://e-enm.org/Synapse/Data/PDFData/2008ENM/enm-32-115.pdf |
work_keys_str_mv |
AT kwihyunbae lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT jungbeomseo lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT yunajung lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT hyeyoungseo lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT sunheekang lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT huijeonjeon lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT jaemanlee lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT sungwoolee lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT junggukkim lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT inkyulee lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT gwonsoojung lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice AT keungyupark lobeglitazoneanovelperoxisomeproliferatoractivatedreceptorgagonistattenuatesrenalfibrosiscausedbyunilateralureteralobstructioninmice |
_version_ |
1725589014093758464 |