Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice

Abstract Carnitine/organic cation transporter 1 (OCTN1) is the only known uptake transporter for ergothioneine which is a food-derived strong antioxidant amino acid that is absorbed by OCTN1. We previously reported the roles of OCTN1/ergothioneine in the progression of kidney fibrosis in ischemic ki...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shohei Makiishi, Kengo Furuichi, Yuta Yamamura, Keisuke Sako, Yasuyuki Shinozaki, Tadashi Toyama, Shinji Kitajima, Yasunori Iwata, Norihiko Sakai, Miho Shimizu, Tomoko Hirose-Sugiura, Shuichi Kaneko, Yukio Kato, Takashi Wada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/33ff7b36717046dea11ba4198bc3f989
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:33ff7b36717046dea11ba4198bc3f989
record_format	dspace
spelling	oai:doaj.org-article:33ff7b36717046dea11ba4198bc3f9892021-12-02T13:41:43ZCarnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice10.1038/s41598-021-88724-42045-2322https://doaj.org/article/33ff7b36717046dea11ba4198bc3f9892021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88724-4https://doaj.org/toc/2045-2322Abstract Carnitine/organic cation transporter 1 (OCTN1) is the only known uptake transporter for ergothioneine which is a food-derived strong antioxidant amino acid that is absorbed by OCTN1. We previously reported the roles of OCTN1/ergothioneine in the progression of kidney fibrosis in ischemic kidney disease. In this study, we evaluated the roles of OCTN1 in the progression of diabetic kidney disease. A diabetic kidney disease model was induced in octn1 knockout and wild-type mice by streptozotocin (STZ). Oxidative stress, represented by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), were higher in the octn1 knockout mice. Azan- and Sirius red-positive areas increased significantly in the octn1 knockout mice. Gene expression was evaluated by cluster analysis, and shown to be different in the octn1 knockout mice compared with the wild-type mice. In a pathway analysis, the pathway associated with the cytoskeleton and cell adhesion increased. In accordance with interstitial fibrosis in octn1 knockout mice, gene expression of moesin in the injured kidney, known as an associated protein of cytoskeleton and cell membranes, was doubled 28 weeks after STZ injection. In addition, the moesin protein was expressed in a part of α-SMA-positive renal tubular epithelial cells. These findings were confirmed by cultured murine proximal tubular epithelial cells: The expression of moesin was induced under oxidative stress with hydrogen peroxide. These data indicate that OCTN1 would play some roles in progression of interstitial fibrosis under oxidative stress via moesin expression in diabetic kidney disease.Shohei MakiishiKengo FuruichiYuta YamamuraKeisuke SakoYasuyuki ShinozakiTadashi ToyamaShinji KitajimaYasunori IwataNorihiko SakaiMiho ShimizuTomoko Hirose-SugiuraShuichi KanekoYukio KatoTakashi WadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shohei Makiishi Kengo Furuichi Yuta Yamamura Keisuke Sako Yasuyuki Shinozaki Tadashi Toyama Shinji Kitajima Yasunori Iwata Norihiko Sakai Miho Shimizu Tomoko Hirose-Sugiura Shuichi Kaneko Yukio Kato Takashi Wada Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
description	Abstract Carnitine/organic cation transporter 1 (OCTN1) is the only known uptake transporter for ergothioneine which is a food-derived strong antioxidant amino acid that is absorbed by OCTN1. We previously reported the roles of OCTN1/ergothioneine in the progression of kidney fibrosis in ischemic kidney disease. In this study, we evaluated the roles of OCTN1 in the progression of diabetic kidney disease. A diabetic kidney disease model was induced in octn1 knockout and wild-type mice by streptozotocin (STZ). Oxidative stress, represented by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), were higher in the octn1 knockout mice. Azan- and Sirius red-positive areas increased significantly in the octn1 knockout mice. Gene expression was evaluated by cluster analysis, and shown to be different in the octn1 knockout mice compared with the wild-type mice. In a pathway analysis, the pathway associated with the cytoskeleton and cell adhesion increased. In accordance with interstitial fibrosis in octn1 knockout mice, gene expression of moesin in the injured kidney, known as an associated protein of cytoskeleton and cell membranes, was doubled 28 weeks after STZ injection. In addition, the moesin protein was expressed in a part of α-SMA-positive renal tubular epithelial cells. These findings were confirmed by cultured murine proximal tubular epithelial cells: The expression of moesin was induced under oxidative stress with hydrogen peroxide. These data indicate that OCTN1 would play some roles in progression of interstitial fibrosis under oxidative stress via moesin expression in diabetic kidney disease.
format	article
author	Shohei Makiishi Kengo Furuichi Yuta Yamamura Keisuke Sako Yasuyuki Shinozaki Tadashi Toyama Shinji Kitajima Yasunori Iwata Norihiko Sakai Miho Shimizu Tomoko Hirose-Sugiura Shuichi Kaneko Yukio Kato Takashi Wada
author_facet	Shohei Makiishi Kengo Furuichi Yuta Yamamura Keisuke Sako Yasuyuki Shinozaki Tadashi Toyama Shinji Kitajima Yasunori Iwata Norihiko Sakai Miho Shimizu Tomoko Hirose-Sugiura Shuichi Kaneko Yukio Kato Takashi Wada
author_sort	Shohei Makiishi
title	Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
title_short	Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
title_full	Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
title_fullStr	Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
title_full_unstemmed	Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
title_sort	carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/33ff7b36717046dea11ba4198bc3f989
work_keys_str_mv	AT shoheimakiishi carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT kengofuruichi carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT yutayamamura carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT keisukesako carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT yasuyukishinozaki carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT tadashitoyama carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT shinjikitajima carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT yasunoriiwata carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT norihikosakai carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT mihoshimizu carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT tomokohirosesugiura carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT shuichikaneko carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT yukiokato carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice AT takashiwada carnitineorganiccationtransporter1precipitatestheprogressionofinterstitialfibrosisthroughoxidativestressindiabeticnephropathyinmice
_version_	1718392548057153536

Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice

Ejemplares similares