Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy

Abstract We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determine...

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Autores principales:	Ying Fan, Jing Zhang, Wenzhen Xiao, Kyung Lee, Zhengzhe Li, Jiejun Wen, Li He, Dingkun Gui, Rui Xue, Guihua Jian, Xiaohua Sheng, John Cijiang He, Niansong Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6552ee6c30a348679ffdcd2eba99d737
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spelling	oai:doaj.org-article:6552ee6c30a348679ffdcd2eba99d7372021-12-02T12:32:46ZRtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy10.1038/s41598-017-00305-62045-2322https://doaj.org/article/6552ee6c30a348679ffdcd2eba99d7372017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00305-6https://doaj.org/toc/2045-2322Abstract We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress. We found increased expression of RTN1A and ER stress markers in the kidney of db/db-Unx mice. Treatment of TUDCA not only attenuated proteinuria and kidney histological changes, but also ameliorated podocyte and glomeruli injury in diabetic mice, which were associated with reduction of RTN1A and ER stress marker expression in the podocytes of TUDCA-treated mice. In vitro, we showed RTN1A mediates albumin-induced ER stress and apoptosis in human podocytes. A positive feedback loop between RTN1A and CHOP was found leading to an enhanced ER stress in podocytes. Our data suggest that ER stress plays a major role in podocyte injury in DN and RTN1A might be a key regulator of ER stress in podocytes.Ying FanJing ZhangWenzhen XiaoKyung LeeZhengzhe LiJiejun WenLi HeDingkun GuiRui XueGuihua JianXiaohua ShengJohn Cijiang HeNiansong WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying Fan Jing Zhang Wenzhen Xiao Kyung Lee Zhengzhe Li Jiejun Wen Li He Dingkun Gui Rui Xue Guihua Jian Xiaohua Sheng John Cijiang He Niansong Wang Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy
description	Abstract We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress. We found increased expression of RTN1A and ER stress markers in the kidney of db/db-Unx mice. Treatment of TUDCA not only attenuated proteinuria and kidney histological changes, but also ameliorated podocyte and glomeruli injury in diabetic mice, which were associated with reduction of RTN1A and ER stress marker expression in the podocytes of TUDCA-treated mice. In vitro, we showed RTN1A mediates albumin-induced ER stress and apoptosis in human podocytes. A positive feedback loop between RTN1A and CHOP was found leading to an enhanced ER stress in podocytes. Our data suggest that ER stress plays a major role in podocyte injury in DN and RTN1A might be a key regulator of ER stress in podocytes.
format	article
author	Ying Fan Jing Zhang Wenzhen Xiao Kyung Lee Zhengzhe Li Jiejun Wen Li He Dingkun Gui Rui Xue Guihua Jian Xiaohua Sheng John Cijiang He Niansong Wang
author_facet	Ying Fan Jing Zhang Wenzhen Xiao Kyung Lee Zhengzhe Li Jiejun Wen Li He Dingkun Gui Rui Xue Guihua Jian Xiaohua Sheng John Cijiang He Niansong Wang
author_sort	Ying Fan
title	Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy
title_short	Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy
title_full	Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy
title_fullStr	Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy
title_full_unstemmed	Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy
title_sort	rtn1a-mediated endoplasmic reticulum stress in podocyte injury and diabetic nephropathy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6552ee6c30a348679ffdcd2eba99d737
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Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy

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