Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway

Abstract Background: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of k...

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Autores principales:	Zhao,Xiaoying, Zhang,Erfei, Ren,Xiaofen, Bai,Xiaoli, Wang,Dongming, Bai,Ling, Luo,Danlei, Guo,Zheng, Wang,Qiang, Yang,Jianxin
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2020
Materias:	Ischemia-reperfusion injury Edaravone JAK/STAT Mitochondria
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100224
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spelling	oai:scielo:S0716-976020200001002242020-07-27Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathwayZhao,XiaoyingZhang,ErfeiRen,XiaofenBai,XiaoliWang,DongmingBai,LingLuo,DanleiGuo,ZhengWang,QiangYang,Jianxin Ischemia-reperfusion injury Edaravone JAK/STAT Mitochondria Abstract Background: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. Methods: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔΨm) measurement. Results: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney ΔΨm. Conclusion: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.53 20202020-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100224en10.1186/s40659-020-00297-0
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Ischemia-reperfusion injury Edaravone JAK/STAT Mitochondria
spellingShingle	Ischemia-reperfusion injury Edaravone JAK/STAT Mitochondria Zhao,Xiaoying Zhang,Erfei Ren,Xiaofen Bai,Xiaoli Wang,Dongming Bai,Ling Luo,Danlei Guo,Zheng Wang,Qiang Yang,Jianxin Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway
description	Abstract Background: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. Methods: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔΨm) measurement. Results: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney ΔΨm. Conclusion: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
author	Zhao,Xiaoying Zhang,Erfei Ren,Xiaofen Bai,Xiaoli Wang,Dongming Bai,Ling Luo,Danlei Guo,Zheng Wang,Qiang Yang,Jianxin
author_facet	Zhao,Xiaoying Zhang,Erfei Ren,Xiaofen Bai,Xiaoli Wang,Dongming Bai,Ling Luo,Danlei Guo,Zheng Wang,Qiang Yang,Jianxin
author_sort	Zhao,Xiaoying
title	Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway
title_short	Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway
title_full	Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway
title_fullStr	Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway
title_full_unstemmed	Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway
title_sort	edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the jak/stat pathway
publisher	Sociedad de Biología de Chile
publishDate	2020
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100224
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Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway

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