Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells

<p dir="ltr">Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerge...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Olfa Khalifa (10914452) (author)
مؤلفون آخرون: Khalid Ouararhni (3145734) (author), Khaoula Errafii (10914446) (author), Nehad M. Alajez (7397276) (author), Abdelilah Arredouani (10914455) (author)
منشور في: 2023
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author Olfa Khalifa (10914452)
author2 Khalid Ouararhni (3145734)
Khaoula Errafii (10914446)
Nehad M. Alajez (7397276)
Abdelilah Arredouani (10914455)
author2_role author
author
author
author
author_facet Olfa Khalifa (10914452)
Khalid Ouararhni (3145734)
Khaoula Errafii (10914446)
Nehad M. Alajez (7397276)
Abdelilah Arredouani (10914455)
author_role author
dc.creator.none.fl_str_mv Olfa Khalifa (10914452)
Khalid Ouararhni (3145734)
Khaoula Errafii (10914446)
Nehad M. Alajez (7397276)
Abdelilah Arredouani (10914455)
dc.date.none.fl_str_mv 2023-07-18T09:00:00Z
dc.identifier.none.fl_str_mv 10.3390/ijms241411606
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Targeted_MicroRNA_Profiling_Reveals_That_Exendin-4_Modulates_the_Expression_of_Several_MicroRNAs_to_Reduce_Steatosis_in_HepG2_Cells/26640190
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
steatosis
NAFLD
exendin-4
miRNAs
HepG2
GLP-1R agonist
dc.title.none.fl_str_mv Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from control, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment pathway analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, insulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigation.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms241411606" target="_blank">https://dx.doi.org/10.3390/ijms241411606</a></p>
eu_rights_str_mv openAccess
id Manara2_2487519f37fa1f5bd404c1870b477e89
identifier_str_mv 10.3390/ijms241411606
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/26640190
publishDate 2023
repository.mail.fl_str_mv
repository.name.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 CellsOlfa Khalifa (10914452)Khalid Ouararhni (3145734)Khaoula Errafii (10914446)Nehad M. Alajez (7397276)Abdelilah Arredouani (10914455)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesClinical sciencessteatosisNAFLDexendin-4miRNAsHepG2GLP-1R agonist<p dir="ltr">Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from control, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment pathway analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, insulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigation.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms241411606" target="_blank">https://dx.doi.org/10.3390/ijms241411606</a></p>2023-07-18T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms241411606https://figshare.com/articles/journal_contribution/Targeted_MicroRNA_Profiling_Reveals_That_Exendin-4_Modulates_the_Expression_of_Several_MicroRNAs_to_Reduce_Steatosis_in_HepG2_Cells/26640190CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/266401902023-07-18T09:00:00Z
spellingShingle Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
Olfa Khalifa (10914452)
Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
steatosis
NAFLD
exendin-4
miRNAs
HepG2
GLP-1R agonist
status_str publishedVersion
title Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
title_full Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
title_fullStr Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
title_full_unstemmed Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
title_short Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
title_sort Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells
topic Biological sciences
Biochemistry and cell biology
Genetics
Biomedical and clinical sciences
Clinical sciences
steatosis
NAFLD
exendin-4
miRNAs
HepG2
GLP-1R agonist