Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis

Junjie Li,* Lijia Peng,* Wenya Bai, Peihua Peng, Wendong Chen, Wei Yang, Jianlin Shao Department of Anesthesiology, First Affiliated Hospital, Kunming Medical University, Kunming City, 650032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianlin...

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Autores principales:	Li J, Peng L, Bai W, Peng P, Chen W, Yang W, Shao J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cerebral ischemia/reperfusion biliverdin mir-27a-3p rgs1 inflammation apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/57d0029e3bc5437793bd7781fd68ed0f
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spelling	oai:doaj.org-article:57d0029e3bc5437793bd7781fd68ed0f2021-12-02T16:41:24ZBiliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis1178-2021https://doaj.org/article/57d0029e3bc5437793bd7781fd68ed0f2021-04-01T00:00:00Zhttps://www.dovepress.com/biliverdin-protects-against-cerebral-ischemiareperfusion-injury-by-reg-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Junjie Li,* Lijia Peng,* Wenya Bai, Peihua Peng, Wendong Chen, Wei Yang, Jianlin Shao Department of Anesthesiology, First Affiliated Hospital, Kunming Medical University, Kunming City, 650032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianlin ShaoDepartment of Anesthesiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wuhua, Kunming, Yunnan, 650000, People’s Republic of ChinaTel +86-871-6532488-2755Email cmushaojlmz@163.comBackground: We have previously demonstrated that biliverdin has neuroprotective effects that ameliorate cerebral ischemia/reperfusion (I/R) injury in rats. However, the underlying mechanism is unknown. This study aimed at elucidating on the modulatory role of miR-27a-3p on Rgs1 as a mechanism by which biliverdin affects cerebral I/R injury.Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to establish I/R rat models while oxygen glucose deprivation/reoxygenation (OGD/R) was used to induce hippocampal neurons to establish I/R models in vitro. Infarct volume was assessed by TTC staining. Apoptotic analyses of ischemic cortical neurons and cells were performed by TUNEL staining and flow cytometry, respectively. Cell viability was assessed by the CCK-8 assay while the target of miR-27a-3p was determined by double luciferase reporter assay. Relative expression levels of miR-27a-3p and Rgs1 (in vivo and in vitro) as well as markers of inflammation and apoptosis (in vitro) were detected by RT-qPCR. Then, Elisa and western blot were used to assess protein expression levels of inflammatory and apoptotic markers in vitro.Results: Biliverdin suppressed inflammation and apoptosis in hippocampal neurons upon OGD/R, and reduced cerebral infarction volume as well as apoptosis in the MCAO/R rat model. Furthermore, biliverdin upregulated miR-27a-3p and downregulated hippocampal neuron Rgs1 after OGD/R as well as in rat brain tissues after cerebral I/R. Bioinformatic analysis revealed an miR-27a-3p docking site in the 3ʹ-UTR region of Rgs1. Luciferase reporter assays showed that Rgs1 is an miR-27a-3p target. Moreover, miR-27a-3p upregulation inhibited OGD/R-triggered inflammation and suppressed neuronal apoptosis. Rgs1 knockdown suppressed OGD/R-triggered inflammation and decreased neuronal apoptosis while miR-27a-3p downregulation reversed the protective effect of Rgs1 knockdown. Moreover, miR-27a-3p overexpression and Rgs1 silencing suppressed NF-κB (p65) expression.Conclusion: Biliverdin protects against cerebral I/R injury by regulating the miR-27a-3p/Rgs1 axis, thereby inhibiting inflammation and apoptosis.Keywords: cerebral ischemia/reperfusion, biliverdin, miR-27a-3p, Rgs1, inflammation, apoptosisLi JPeng LBai WPeng PChen WYang WShao JDove Medical Pressarticlecerebral ischemia/reperfusionbiliverdinmir-27a-3prgs1inflammationapoptosisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 1165-1181 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cerebral ischemia/reperfusion biliverdin mir-27a-3p rgs1 inflammation apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	cerebral ischemia/reperfusion biliverdin mir-27a-3p rgs1 inflammation apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Li J Peng L Bai W Peng P Chen W Yang W Shao J Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis
description	Junjie Li,* Lijia Peng,* Wenya Bai, Peihua Peng, Wendong Chen, Wei Yang, Jianlin Shao Department of Anesthesiology, First Affiliated Hospital, Kunming Medical University, Kunming City, 650032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianlin ShaoDepartment of Anesthesiology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wuhua, Kunming, Yunnan, 650000, People’s Republic of ChinaTel +86-871-6532488-2755Email cmushaojlmz@163.comBackground: We have previously demonstrated that biliverdin has neuroprotective effects that ameliorate cerebral ischemia/reperfusion (I/R) injury in rats. However, the underlying mechanism is unknown. This study aimed at elucidating on the modulatory role of miR-27a-3p on Rgs1 as a mechanism by which biliverdin affects cerebral I/R injury.Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to establish I/R rat models while oxygen glucose deprivation/reoxygenation (OGD/R) was used to induce hippocampal neurons to establish I/R models in vitro. Infarct volume was assessed by TTC staining. Apoptotic analyses of ischemic cortical neurons and cells were performed by TUNEL staining and flow cytometry, respectively. Cell viability was assessed by the CCK-8 assay while the target of miR-27a-3p was determined by double luciferase reporter assay. Relative expression levels of miR-27a-3p and Rgs1 (in vivo and in vitro) as well as markers of inflammation and apoptosis (in vitro) were detected by RT-qPCR. Then, Elisa and western blot were used to assess protein expression levels of inflammatory and apoptotic markers in vitro.Results: Biliverdin suppressed inflammation and apoptosis in hippocampal neurons upon OGD/R, and reduced cerebral infarction volume as well as apoptosis in the MCAO/R rat model. Furthermore, biliverdin upregulated miR-27a-3p and downregulated hippocampal neuron Rgs1 after OGD/R as well as in rat brain tissues after cerebral I/R. Bioinformatic analysis revealed an miR-27a-3p docking site in the 3ʹ-UTR region of Rgs1. Luciferase reporter assays showed that Rgs1 is an miR-27a-3p target. Moreover, miR-27a-3p upregulation inhibited OGD/R-triggered inflammation and suppressed neuronal apoptosis. Rgs1 knockdown suppressed OGD/R-triggered inflammation and decreased neuronal apoptosis while miR-27a-3p downregulation reversed the protective effect of Rgs1 knockdown. Moreover, miR-27a-3p overexpression and Rgs1 silencing suppressed NF-κB (p65) expression.Conclusion: Biliverdin protects against cerebral I/R injury by regulating the miR-27a-3p/Rgs1 axis, thereby inhibiting inflammation and apoptosis.Keywords: cerebral ischemia/reperfusion, biliverdin, miR-27a-3p, Rgs1, inflammation, apoptosis
format	article
author	Li J Peng L Bai W Peng P Chen W Yang W Shao J
author_facet	Li J Peng L Bai W Peng P Chen W Yang W Shao J
author_sort	Li J
title	Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis
title_short	Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis
title_full	Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis
title_fullStr	Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis
title_full_unstemmed	Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis
title_sort	biliverdin protects against cerebral ischemia/reperfusion injury by regulating the mir-27a-3p/rgs1 axis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/57d0029e3bc5437793bd7781fd68ed0f
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Biliverdin Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating the miR-27a-3p/Rgs1 Axis

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