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Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation
Diabetes is an inflammatory disease that induces pancreatic islet dysfunction. However, to the best of our knowledge, the potential underlying molecular mechanisms of this inflammatory process remains unknown. The present study investigated microRNA (miRNA/miR) and protein expression profiles throug...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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D.A. Spandidos
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739849/ https://www.ncbi.nlm.nih.gov/pubmed/33335585 http://dx.doi.org/10.3892/etm.2020.9554 |
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author | Ding, Yipei Zhong, Jin Wang, Yangyang Xie, Weidong |
author_facet | Ding, Yipei Zhong, Jin Wang, Yangyang Xie, Weidong |
author_sort | Ding, Yipei |
collection | PubMed |
description | Diabetes is an inflammatory disease that induces pancreatic islet dysfunction. However, to the best of our knowledge, the potential underlying molecular mechanisms of this inflammatory process remains unknown. The present study investigated microRNA (miRNA/miR) and protein expression profiles through proteomics and miRNA-omics. Lipopolysaccharide-induced macrophage cell medium (LRM) was used to stimulate inflammation in mouse Beta-TC-6 islet cells. Protein analysis revealed that 87 proteins were upregulated and 42 proteins were downregulated in LRM-treated Beta-TC-6 cells compared with control cells. Additionally, miRNA analysis revealed that 11 miRNAs were upregulated, while 28 miRNAs were downregulated in LRM-treated Beta-TC-6 cells compared with control cells. Islet cells exposed to inflammation exhibited markedly downregulated protein levels of transcription factor MafA, pancreatic and duodenal homeobox 1, paired box 6, homeobox protein Nkx-2.2, synaptosomal-associated protein 25, glucagon and insulin-2, while the expression of miR-146a-5p and miR-21a-5p were upregulated. It was also determined that upregulated miR-146a-5p and miR-21a-5p levels may be mediated by NF-κB activation. The downregulation of islet functional factor mRNA was partially reversed by treating islet cells with an inhibitor of miR-21a-5p. However, treatment with an miR-146a-5p inhibitor did not exert the same effect. Overall, the present study determined the molecular profiles of islet cell inflammation based on proteomics and miRNA-omics, and indicated that the proteins and miRNAs with altered expressions may form a large network that serves a role in islet dysfunction. Particularly, miR-21a-5p upregulation in response to inflammation may contribute to islet cell dysfunction. However, how these miRNAs regulated the expression of certain mRNAs and proteins in islet cell inflammation requires further investigation. |
format | Online Article Text |
id | pubmed-7739849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-77398492020-12-16 Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation Ding, Yipei Zhong, Jin Wang, Yangyang Xie, Weidong Exp Ther Med Articles Diabetes is an inflammatory disease that induces pancreatic islet dysfunction. However, to the best of our knowledge, the potential underlying molecular mechanisms of this inflammatory process remains unknown. The present study investigated microRNA (miRNA/miR) and protein expression profiles through proteomics and miRNA-omics. Lipopolysaccharide-induced macrophage cell medium (LRM) was used to stimulate inflammation in mouse Beta-TC-6 islet cells. Protein analysis revealed that 87 proteins were upregulated and 42 proteins were downregulated in LRM-treated Beta-TC-6 cells compared with control cells. Additionally, miRNA analysis revealed that 11 miRNAs were upregulated, while 28 miRNAs were downregulated in LRM-treated Beta-TC-6 cells compared with control cells. Islet cells exposed to inflammation exhibited markedly downregulated protein levels of transcription factor MafA, pancreatic and duodenal homeobox 1, paired box 6, homeobox protein Nkx-2.2, synaptosomal-associated protein 25, glucagon and insulin-2, while the expression of miR-146a-5p and miR-21a-5p were upregulated. It was also determined that upregulated miR-146a-5p and miR-21a-5p levels may be mediated by NF-κB activation. The downregulation of islet functional factor mRNA was partially reversed by treating islet cells with an inhibitor of miR-21a-5p. However, treatment with an miR-146a-5p inhibitor did not exert the same effect. Overall, the present study determined the molecular profiles of islet cell inflammation based on proteomics and miRNA-omics, and indicated that the proteins and miRNAs with altered expressions may form a large network that serves a role in islet dysfunction. Particularly, miR-21a-5p upregulation in response to inflammation may contribute to islet cell dysfunction. However, how these miRNAs regulated the expression of certain mRNAs and proteins in islet cell inflammation requires further investigation. D.A. Spandidos 2021-02 2020-12-03 /pmc/articles/PMC7739849/ /pubmed/33335585 http://dx.doi.org/10.3892/etm.2020.9554 Text en Copyright: © Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Ding, Yipei Zhong, Jin Wang, Yangyang Xie, Weidong Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
title | Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
title_full | Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
title_fullStr | Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
title_full_unstemmed | Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
title_short | Proteomic and microRNA-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
title_sort | proteomic and microrna-omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739849/ https://www.ncbi.nlm.nih.gov/pubmed/33335585 http://dx.doi.org/10.3892/etm.2020.9554 |
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