Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress
<p dir="ltr">Overactivation of the renin–angiotensin system (RAS) during obesity disrupts adipocyte metabolic homeostasis and induces endoplasmic reticulum (ER) stress and inflammation; however, underlying mechanisms are not well known. We propose that overexpression of angiotensinog...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2020
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| _version_ | 1864513515818057728 |
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| author | Kalhara R. Menikdiwela (18566698) |
| author2 | Latha Ramalingam (18300808) Mostafa M. Abbas (17058093) Halima Bensmail (10400) Shane Scoggin (18566701) Nishan S. Kalupahana (18566704) Asha Palat (18566707) Preethi Gunaratne (8410134) Naima Moustaid-Moussa (66960) |
| author2_role | author author author author author author author author |
| author_facet | Kalhara R. Menikdiwela (18566698) Latha Ramalingam (18300808) Mostafa M. Abbas (17058093) Halima Bensmail (10400) Shane Scoggin (18566701) Nishan S. Kalupahana (18566704) Asha Palat (18566707) Preethi Gunaratne (8410134) Naima Moustaid-Moussa (66960) |
| author_role | author |
| dc.creator.none.fl_str_mv | Kalhara R. Menikdiwela (18566698) Latha Ramalingam (18300808) Mostafa M. Abbas (17058093) Halima Bensmail (10400) Shane Scoggin (18566701) Nishan S. Kalupahana (18566704) Asha Palat (18566707) Preethi Gunaratne (8410134) Naima Moustaid-Moussa (66960) |
| dc.date.none.fl_str_mv | 2020-05-26T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/cells9061327 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Role_of_microRNA_690_in_Mediating_Angiotensin_II_Effects_on_Inflammation_and_Endoplasmic_Reticulum_Stress/25835257 |
| 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 Metabolic medicine adipocytes renin–angiotensin system (RAS) obesity miR-690 endoplasmic reticulum (ER) stress inflammation |
| dc.title.none.fl_str_mv | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Overactivation of the renin–angiotensin system (RAS) during obesity disrupts adipocyte metabolic homeostasis and induces endoplasmic reticulum (ER) stress and inflammation; however, underlying mechanisms are not well known. We propose that overexpression of angiotensinogen (Agt), the precursor protein of RAS in adipose tissue or treatment of adipocytes with Angiotensin II (Ang II), RAS bioactive hormone, alters specific microRNAs (miRNA), that target ER stress and inflammation leading to adipocyte dysfunction. Epididymal white adipose tissue (WAT) from B6 wild type (Wt) and transgenic male mice overexpressing Agt (Agt-Tg) in adipose tissue and adipocytes treated with Ang II were used. Small RNA sequencing and microarray in WAT identified differentially expressed miRNAs and genes, out of which miR-690 and mitogen-activated protein kinase kinase 3 (MAP2K3) were validated as significantly up- and down-regulated, respectively, in Agt-Tg, and in Ang II-treated adipocytes compared to respective controls. Additionally, the direct regulatory role of miR-690 on MAP2K3 was confirmed using mimic, inhibitors and dual-luciferase reporter assay. Downstream protein targets of MAP2K3 which include p38, NF-κB, IL-6 and CHOP were all reduced. These results indicate a critical post-transcriptional role for miR-690 in inflammation and ER stress. In conclusion, miR-690 plays a protective function and could be a useful target to reduce obesity.</p><h2>Other Information</h2><p dir="ltr">Published in: Cells<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/cells9061327" target="_blank">https://dx.doi.org/10.3390/cells9061327</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_38fc4622bc724ae754ac85e82162e5b7 |
| identifier_str_mv | 10.3390/cells9061327 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25835257 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum StressKalhara R. Menikdiwela (18566698)Latha Ramalingam (18300808)Mostafa M. Abbas (17058093)Halima Bensmail (10400)Shane Scoggin (18566701)Nishan S. Kalupahana (18566704)Asha Palat (18566707)Preethi Gunaratne (8410134)Naima Moustaid-Moussa (66960)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesMetabolic medicineadipocytesrenin–angiotensin system (RAS)obesitymiR-690endoplasmic reticulum (ER) stressinflammation<p dir="ltr">Overactivation of the renin–angiotensin system (RAS) during obesity disrupts adipocyte metabolic homeostasis and induces endoplasmic reticulum (ER) stress and inflammation; however, underlying mechanisms are not well known. We propose that overexpression of angiotensinogen (Agt), the precursor protein of RAS in adipose tissue or treatment of adipocytes with Angiotensin II (Ang II), RAS bioactive hormone, alters specific microRNAs (miRNA), that target ER stress and inflammation leading to adipocyte dysfunction. Epididymal white adipose tissue (WAT) from B6 wild type (Wt) and transgenic male mice overexpressing Agt (Agt-Tg) in adipose tissue and adipocytes treated with Ang II were used. Small RNA sequencing and microarray in WAT identified differentially expressed miRNAs and genes, out of which miR-690 and mitogen-activated protein kinase kinase 3 (MAP2K3) were validated as significantly up- and down-regulated, respectively, in Agt-Tg, and in Ang II-treated adipocytes compared to respective controls. Additionally, the direct regulatory role of miR-690 on MAP2K3 was confirmed using mimic, inhibitors and dual-luciferase reporter assay. Downstream protein targets of MAP2K3 which include p38, NF-κB, IL-6 and CHOP were all reduced. These results indicate a critical post-transcriptional role for miR-690 in inflammation and ER stress. In conclusion, miR-690 plays a protective function and could be a useful target to reduce obesity.</p><h2>Other Information</h2><p dir="ltr">Published in: Cells<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/cells9061327" target="_blank">https://dx.doi.org/10.3390/cells9061327</a></p>2020-05-26T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/cells9061327https://figshare.com/articles/journal_contribution/Role_of_microRNA_690_in_Mediating_Angiotensin_II_Effects_on_Inflammation_and_Endoplasmic_Reticulum_Stress/25835257CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258352572020-05-26T09:00:00Z |
| spellingShingle | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress Kalhara R. Menikdiwela (18566698) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Metabolic medicine adipocytes renin–angiotensin system (RAS) obesity miR-690 endoplasmic reticulum (ER) stress inflammation |
| status_str | publishedVersion |
| title | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| title_full | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| title_fullStr | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| title_full_unstemmed | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| title_short | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| title_sort | Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Metabolic medicine adipocytes renin–angiotensin system (RAS) obesity miR-690 endoplasmic reticulum (ER) stress inflammation |