Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway

Previously, Our study has showed that farrerol can activate Nrf2 and ameliorate cisplatin-induced acute kidney injury (AKI). Mitophagy reportedly can prevent diabetic nephropathy, cisplatin-induced AKI and other related nephropathy. In this study, we evaluated the correlation between mitophagy and t...

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Autores principales:	Ning Ma, Zhentong wei, Jianqiang Hu, Wenjing Gu, Xinxin Ci
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	chronic kidney disease mitophagy Nrf2 PINK1 acute kidney injury Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4f7ed3b9b3a6484b99ac75349fcaaabc
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spelling	oai:doaj.org-article:4f7ed3b9b3a6484b99ac75349fcaaabc2021-11-11T06:18:42ZFarrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway1663-981210.3389/fphar.2021.768700https://doaj.org/article/4f7ed3b9b3a6484b99ac75349fcaaabc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.768700/fullhttps://doaj.org/toc/1663-9812Previously, Our study has showed that farrerol can activate Nrf2 and ameliorate cisplatin-induced acute kidney injury (AKI). Mitophagy reportedly can prevent diabetic nephropathy, cisplatin-induced AKI and other related nephropathy. In this study, we evaluated the correlation between mitophagy and the protective effect of the Nrf2 activator farrerol on cisplatin-induced CKD by using C57BL/6 wild-type and Nrf2 knockout mice. We confirmed that Nrf2 and PINK1/Parkin-mediated mitophagy was significantly increased on the 3rd day of cisplatin stimulation but was reduced on the 38th day of cisplatin stimulation. Similar to previous results, farrerol activated Nrf2 on the 38th day of cisplatin administration, subsequently stimulating the Nrf2-targeted antioxidant enzymes HO-1 and NQO1. In addition, farrerol triggered PINK1/Parkin-mediated mitophagy by recruiting the receptor proteins LC3 and p62/SQSTM1, thereby eliminating damaged mitochondria. Furthermore, genetic deletion of Nrf2 reduced PINK1/Parkin-mediated mitophagy activation and led to increased renal tubular necrosis and renal fibrosis. We also found that farrerol alleviated inflammation and renal fibrosis by inhibiting p-NF-κB/NLRP3 and TGF-β/Smad signaling. These data indicated that farrerol effectively inhibited cisplatin-induced inflammation and renal fibrosis by activating Nrf2 and PINK1/Parkin-mediated mitophagy, which provides a potential novel therapeutic target for CKD.Ning MaNing MaZhentong weiJianqiang HuWenjing GuXinxin CiXinxin CiFrontiers Media S.A.articlechronic kidney diseasemitophagyNrf2PINK1acute kidney injuryTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chronic kidney disease mitophagy Nrf2 PINK1 acute kidney injury Therapeutics. Pharmacology RM1-950
spellingShingle	chronic kidney disease mitophagy Nrf2 PINK1 acute kidney injury Therapeutics. Pharmacology RM1-950 Ning Ma Ning Ma Zhentong wei Jianqiang Hu Wenjing Gu Xinxin Ci Xinxin Ci Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
description	Previously, Our study has showed that farrerol can activate Nrf2 and ameliorate cisplatin-induced acute kidney injury (AKI). Mitophagy reportedly can prevent diabetic nephropathy, cisplatin-induced AKI and other related nephropathy. In this study, we evaluated the correlation between mitophagy and the protective effect of the Nrf2 activator farrerol on cisplatin-induced CKD by using C57BL/6 wild-type and Nrf2 knockout mice. We confirmed that Nrf2 and PINK1/Parkin-mediated mitophagy was significantly increased on the 3rd day of cisplatin stimulation but was reduced on the 38th day of cisplatin stimulation. Similar to previous results, farrerol activated Nrf2 on the 38th day of cisplatin administration, subsequently stimulating the Nrf2-targeted antioxidant enzymes HO-1 and NQO1. In addition, farrerol triggered PINK1/Parkin-mediated mitophagy by recruiting the receptor proteins LC3 and p62/SQSTM1, thereby eliminating damaged mitochondria. Furthermore, genetic deletion of Nrf2 reduced PINK1/Parkin-mediated mitophagy activation and led to increased renal tubular necrosis and renal fibrosis. We also found that farrerol alleviated inflammation and renal fibrosis by inhibiting p-NF-κB/NLRP3 and TGF-β/Smad signaling. These data indicated that farrerol effectively inhibited cisplatin-induced inflammation and renal fibrosis by activating Nrf2 and PINK1/Parkin-mediated mitophagy, which provides a potential novel therapeutic target for CKD.
format	article
author	Ning Ma Ning Ma Zhentong wei Jianqiang Hu Wenjing Gu Xinxin Ci Xinxin Ci
author_facet	Ning Ma Ning Ma Zhentong wei Jianqiang Hu Wenjing Gu Xinxin Ci Xinxin Ci
author_sort	Ning Ma
title	Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
title_short	Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
title_full	Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
title_fullStr	Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
title_full_unstemmed	Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway
title_sort	farrerol ameliorated cisplatin-induced chronic kidney disease through mitophagy induction via nrf2/pink1 pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4f7ed3b9b3a6484b99ac75349fcaaabc
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Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway

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