Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin

Astrocytes are major glial cells that play a critical role in brain homeostasis. Abnormalities in astrocytic function, such as hepatic encephalopathy (HE) during acute liver failure, can result in brain death following brain edema and the associated astrocyte swelling. Recently, we have identified a...

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Main Authors: Kenji Kawaguchi, Jonghyuk Park, Takahiro Masaki, Yoshihiro Mezaki, Sae Ochi, Tomokazu Matsuura
Format: Article
Language:English
Published: Elsevier 2020-12-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580820301655
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author Kenji Kawaguchi
Jonghyuk Park
Takahiro Masaki
Yoshihiro Mezaki
Sae Ochi
Tomokazu Matsuura
author_facet Kenji Kawaguchi
Jonghyuk Park
Takahiro Masaki
Yoshihiro Mezaki
Sae Ochi
Tomokazu Matsuura
author_sort Kenji Kawaguchi
collection DOAJ
description Astrocytes are major glial cells that play a critical role in brain homeostasis. Abnormalities in astrocytic function, such as hepatic encephalopathy (HE) during acute liver failure, can result in brain death following brain edema and the associated astrocyte swelling. Recently, we have identified alpha 1-antichymotripsin (ACT) to be a biomarker candidate for HE. ACT induces astrocyte swelling by upregulating aquaporin 4 (AQP4); however, the causal connection between these proteins is not clear yet. In this study, we utilized a microarray profile to screen the differentially expressed genes (DEGs) in astrocytes treated with ACT. We then performed Gene Ontology, REACTOME, and the comprehensive resource of mammalian protein complexes (CORUM) enrichment analyses of the identified DEGs. The results of these analyses indicated that the DEGs were enriched in pathways activating adenylate cyclase (AC)-coupled G protein-coupled receptors (GPCRs) and therefore were involved in the cyclic adenosine monophosphate (cAMP) signaling. These results indicate that ACT may act as a ligand of Gs-GPCRs and subsequently upregulate cAMP. As cAMP is known to upregulate AQP4 in astrocytes, these results suggest that ACT may upregulate AQP4 by activating AC GPCRs and therefore serve as a therapeutic target for acute HE.
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spelling doaj.art-a84064f83b1e440eb6fa0326697026512022-12-21T23:18:59ZengElsevierBiochemistry and Biophysics Reports2405-58082020-12-0124100855Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsinKenji Kawaguchi0Jonghyuk Park1Takahiro Masaki2Yoshihiro Mezaki3Sae Ochi4Tomokazu Matsuura5Corresponding author.; Department of Laboratory Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, JapanDepartment of Laboratory Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, JapanDepartment of Laboratory Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, JapanDepartment of Laboratory Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, JapanDepartment of Laboratory Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, JapanDepartment of Laboratory Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, JapanAstrocytes are major glial cells that play a critical role in brain homeostasis. Abnormalities in astrocytic function, such as hepatic encephalopathy (HE) during acute liver failure, can result in brain death following brain edema and the associated astrocyte swelling. Recently, we have identified alpha 1-antichymotripsin (ACT) to be a biomarker candidate for HE. ACT induces astrocyte swelling by upregulating aquaporin 4 (AQP4); however, the causal connection between these proteins is not clear yet. In this study, we utilized a microarray profile to screen the differentially expressed genes (DEGs) in astrocytes treated with ACT. We then performed Gene Ontology, REACTOME, and the comprehensive resource of mammalian protein complexes (CORUM) enrichment analyses of the identified DEGs. The results of these analyses indicated that the DEGs were enriched in pathways activating adenylate cyclase (AC)-coupled G protein-coupled receptors (GPCRs) and therefore were involved in the cyclic adenosine monophosphate (cAMP) signaling. These results indicate that ACT may act as a ligand of Gs-GPCRs and subsequently upregulate cAMP. As cAMP is known to upregulate AQP4 in astrocytes, these results suggest that ACT may upregulate AQP4 by activating AC GPCRs and therefore serve as a therapeutic target for acute HE.http://www.sciencedirect.com/science/article/pii/S2405580820301655AstrocyteAlpha 1-antichymotripsinArginine vasopressinGPCRcAMPAdenylate cyclase
spellingShingle Kenji Kawaguchi
Jonghyuk Park
Takahiro Masaki
Yoshihiro Mezaki
Sae Ochi
Tomokazu Matsuura
Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin
Biochemistry and Biophysics Reports
Astrocyte
Alpha 1-antichymotripsin
Arginine vasopressin
GPCR
cAMP
Adenylate cyclase
title Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin
title_full Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin
title_fullStr Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin
title_full_unstemmed Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin
title_short Comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy-inducible factor, alpha 1-antichymotripsin
title_sort comprehensive gene expression profiling of human astrocytes treated with a hepatic encephalopathy inducible factor alpha 1 antichymotripsin
topic Astrocyte
Alpha 1-antichymotripsin
Arginine vasopressin
GPCR
cAMP
Adenylate cyclase
url http://www.sciencedirect.com/science/article/pii/S2405580820301655
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