Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspas...

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Autores principales:	Wen Li, Jing Sun, Xiaoxi Zhou, Yue Lu, Wenpeng Cui, Lining Miao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	pyroptosis gasdermin GSDME caspase-3 diabetic nephropathy Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/96fc85df444245219464cf648af0c843
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spelling	oai:doaj.org-article:96fc85df444245219464cf648af0c8432021-11-18T09:57:21ZMini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy1663-981210.3389/fphar.2021.780790https://doaj.org/article/96fc85df444245219464cf648af0c8432021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.780790/fullhttps://doaj.org/toc/1663-9812Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people’s attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.Wen LiJing SunXiaoxi ZhouYue LuWenpeng CuiLining MiaoFrontiers Media S.A.articlepyroptosisgasderminGSDMEcaspase-3diabetic nephropathyTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pyroptosis gasdermin GSDME caspase-3 diabetic nephropathy Therapeutics. Pharmacology RM1-950
spellingShingle	pyroptosis gasdermin GSDME caspase-3 diabetic nephropathy Therapeutics. Pharmacology RM1-950 Wen Li Jing Sun Xiaoxi Zhou Yue Lu Wenpeng Cui Lining Miao Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy
description	Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people’s attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.
format	article
author	Wen Li Jing Sun Xiaoxi Zhou Yue Lu Wenpeng Cui Lining Miao
author_facet	Wen Li Jing Sun Xiaoxi Zhou Yue Lu Wenpeng Cui Lining Miao
author_sort	Wen Li
title	Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy
title_short	Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy
title_full	Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy
title_fullStr	Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy
title_full_unstemmed	Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy
title_sort	mini-review: gsdme-mediated pyroptosis in diabetic nephropathy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/96fc85df444245219464cf648af0c843
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Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

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