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MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons
Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan prot...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358889/ https://www.ncbi.nlm.nih.gov/pubmed/34160889 http://dx.doi.org/10.1111/jcmm.16669 |
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author | Dou, Yunxiao Tan, Yan Yu, Tongya Ma, Xiaoye Zhou, Yuchen Zhao, Yichen Zhao, Yanxin Liu, Xueyuan |
author_facet | Dou, Yunxiao Tan, Yan Yu, Tongya Ma, Xiaoye Zhou, Yuchen Zhao, Yichen Zhao, Yanxin Liu, Xueyuan |
author_sort | Dou, Yunxiao |
collection | PubMed |
description | Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post‐synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β‐dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β‐dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long‐term period, microRNA‐132 (miR‐132) would be down‐regulated in neurons. Matrix Metalloproteinases‐9 (MMP‐9) mRNA, as a target of miR‐132, could be up‐regulated; higher expression and overlay activity of MMP‐9 protein could increase β‐DG protein degradation. In this way, β‐DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes‐induced cognitive dysfunction. |
format | Online Article Text |
id | pubmed-8358889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83588892021-08-15 MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons Dou, Yunxiao Tan, Yan Yu, Tongya Ma, Xiaoye Zhou, Yuchen Zhao, Yichen Zhao, Yanxin Liu, Xueyuan J Cell Mol Med Original Articles Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post‐synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β‐dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β‐dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long‐term period, microRNA‐132 (miR‐132) would be down‐regulated in neurons. Matrix Metalloproteinases‐9 (MMP‐9) mRNA, as a target of miR‐132, could be up‐regulated; higher expression and overlay activity of MMP‐9 protein could increase β‐DG protein degradation. In this way, β‐DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes‐induced cognitive dysfunction. John Wiley and Sons Inc. 2021-06-23 2021-08 /pmc/articles/PMC8358889/ /pubmed/34160889 http://dx.doi.org/10.1111/jcmm.16669 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Dou, Yunxiao Tan, Yan Yu, Tongya Ma, Xiaoye Zhou, Yuchen Zhao, Yichen Zhao, Yanxin Liu, Xueyuan MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons |
title | MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons |
title_full | MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons |
title_fullStr | MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons |
title_full_unstemmed | MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons |
title_short | MiR‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through Matrix Metalloproteinases‐9 up‐regulation in primary neurons |
title_sort | mir‐132 down‐regulates high glucose‐induced β‐dystroglycan degradation through matrix metalloproteinases‐9 up‐regulation in primary neurons |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358889/ https://www.ncbi.nlm.nih.gov/pubmed/34160889 http://dx.doi.org/10.1111/jcmm.16669 |
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