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...
Main Authors: | , , , , , |
---|---|
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 |
_version_ | 1818384443126054912 |
---|---|
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. |
first_indexed | 2024-12-14T03:22:20Z |
format | Article |
id | doaj.art-a84064f83b1e440eb6fa032669702651 |
institution | Directory Open Access Journal |
issn | 2405-5808 |
language | English |
last_indexed | 2024-12-14T03:22:20Z |
publishDate | 2020-12-01 |
publisher | Elsevier |
record_format | Article |
series | Biochemistry and Biophysics Reports |
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 |
work_keys_str_mv | AT kenjikawaguchi comprehensivegeneexpressionprofilingofhumanastrocytestreatedwithahepaticencephalopathyinduciblefactoralpha1antichymotripsin AT jonghyukpark comprehensivegeneexpressionprofilingofhumanastrocytestreatedwithahepaticencephalopathyinduciblefactoralpha1antichymotripsin AT takahiromasaki comprehensivegeneexpressionprofilingofhumanastrocytestreatedwithahepaticencephalopathyinduciblefactoralpha1antichymotripsin AT yoshihiromezaki comprehensivegeneexpressionprofilingofhumanastrocytestreatedwithahepaticencephalopathyinduciblefactoralpha1antichymotripsin AT saeochi comprehensivegeneexpressionprofilingofhumanastrocytestreatedwithahepaticencephalopathyinduciblefactoralpha1antichymotripsin AT tomokazumatsuura comprehensivegeneexpressionprofilingofhumanastrocytestreatedwithahepaticencephalopathyinduciblefactoralpha1antichymotripsin |