Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy

Abstract Aberrant endoplasmic reticulum (ER) stress and autophagy are associated with diabetic nephropathy. Here we investigated the effect of astragaloside IV (AS-IV) on the progression of diabetic nephropathy (DN) and the underlying mechanism involving ER stress and autophagy in streptozotocin (ST...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hengjiang Guo, Yi Wang, Xuemei Zhang, Yingjun Zang, Yang Zhang, Li Wang, Hao Wang, Yunman Wang, Aili Cao, Wen Peng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76f4b33c3d934dc5b3c775fd7c61bd31
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:76f4b33c3d934dc5b3c775fd7c61bd31
record_format	dspace
spelling	oai:doaj.org-article:76f4b33c3d934dc5b3c775fd7c61bd312021-12-02T11:52:59ZAstragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy10.1038/s41598-017-07061-72045-2322https://doaj.org/article/76f4b33c3d934dc5b3c775fd7c61bd312017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07061-7https://doaj.org/toc/2045-2322Abstract Aberrant endoplasmic reticulum (ER) stress and autophagy are associated with diabetic nephropathy. Here we investigated the effect of astragaloside IV (AS-IV) on the progression of diabetic nephropathy (DN) and the underlying mechanism involving ER stress and autophagy in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-incubated podocytes. The diabetic mice developed progressive albuminuria and glomerulosclerosis within 8 weeks, which were significantly ameliorated by AS-IV treatment in a dose-dependent manner. Moreover, diabetes or HG-induced podocyte apoptosis was markedly attenuated by AS-IV, paralleled by a marked remission in ER stress and a remarkable restoration in impaired autophagy, which were associated with a significant improvement in the expression of sarcoendoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) and AMP-activated protein kinase α (AMPKα) phosphorylation, respectively. Knockdown of SERCA2 in podocytes induced ER stress and largely abolished the protective effect of AS-IV, but had no obvious effect on the expression of autophagy-associated proteins. On the other hand, blockade of either autophagy induction or AMPKα activation could also significantly mitigate AS-IV-induced beneficial effect. Collectively, these results suggest that AS-IV prevented the progression of DN, which is mediated at least in part by SERCA2-dependent ER stress attenuation and AMPKα-promoted autophagy induction.Hengjiang GuoYi WangXuemei ZhangYingjun ZangYang ZhangLi WangHao WangYunman WangAili CaoWen PengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hengjiang Guo Yi Wang Xuemei Zhang Yingjun Zang Yang Zhang Li Wang Hao Wang Yunman Wang Aili Cao Wen Peng Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
description	Abstract Aberrant endoplasmic reticulum (ER) stress and autophagy are associated with diabetic nephropathy. Here we investigated the effect of astragaloside IV (AS-IV) on the progression of diabetic nephropathy (DN) and the underlying mechanism involving ER stress and autophagy in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-incubated podocytes. The diabetic mice developed progressive albuminuria and glomerulosclerosis within 8 weeks, which were significantly ameliorated by AS-IV treatment in a dose-dependent manner. Moreover, diabetes or HG-induced podocyte apoptosis was markedly attenuated by AS-IV, paralleled by a marked remission in ER stress and a remarkable restoration in impaired autophagy, which were associated with a significant improvement in the expression of sarcoendoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) and AMP-activated protein kinase α (AMPKα) phosphorylation, respectively. Knockdown of SERCA2 in podocytes induced ER stress and largely abolished the protective effect of AS-IV, but had no obvious effect on the expression of autophagy-associated proteins. On the other hand, blockade of either autophagy induction or AMPKα activation could also significantly mitigate AS-IV-induced beneficial effect. Collectively, these results suggest that AS-IV prevented the progression of DN, which is mediated at least in part by SERCA2-dependent ER stress attenuation and AMPKα-promoted autophagy induction.
format	article
author	Hengjiang Guo Yi Wang Xuemei Zhang Yingjun Zang Yang Zhang Li Wang Hao Wang Yunman Wang Aili Cao Wen Peng
author_facet	Hengjiang Guo Yi Wang Xuemei Zhang Yingjun Zang Yang Zhang Li Wang Hao Wang Yunman Wang Aili Cao Wen Peng
author_sort	Hengjiang Guo
title	Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
title_short	Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
title_full	Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
title_fullStr	Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
title_full_unstemmed	Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
title_sort	astragaloside iv protects against podocyte injury via serca2-dependent er stress reduction and ampkα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/76f4b33c3d934dc5b3c775fd7c61bd31
work_keys_str_mv	AT hengjiangguo astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT yiwang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT xuemeizhang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT yingjunzang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT yangzhang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT liwang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT haowang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT yunmanwang astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT ailicao astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy AT wenpeng astragalosideivprotectsagainstpodocyteinjuryviaserca2dependenterstressreductionandampkaregulatedautophagyinductioninstreptozotocininduceddiabeticnephropathy
_version_	1718394933299118080

Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy

Ejemplares similares