Cargando…
Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway
Diabetic encephalopathy (DE) is a global concern and Gordian knot worldwide. miRNA-132 (miR-132) is a class of negative gene regulators that promote diabetic pathologic mechanisms and its complications. However, the molecular mechanisms of miR-132 in DE are elusive, thus an alternative therapeutic s...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906212/ https://www.ncbi.nlm.nih.gov/pubmed/33406505 http://dx.doi.org/10.18632/aging.202418 |
_version_ | 1783655249242750976 |
---|---|
author | Shi, Li Zhang, Rui Li, Tian Han, Xue Yuan, Nannan Jiang, Lei Zhou, Huimin Xu, Shunjiang |
author_facet | Shi, Li Zhang, Rui Li, Tian Han, Xue Yuan, Nannan Jiang, Lei Zhou, Huimin Xu, Shunjiang |
author_sort | Shi, Li |
collection | PubMed |
description | Diabetic encephalopathy (DE) is a global concern and Gordian knot worldwide. miRNA-132 (miR-132) is a class of negative gene regulators that promote diabetic pathologic mechanisms and its complications. However, the molecular mechanisms of miR-132 in DE are elusive, thus an alternative therapeutic strategy is urgently in demand. The present study explored the protective effect and the underlying mechanism of miR-132 on DE via the GSK-β/Tau signaling pathway. Experimentally, a type 2 DM rat model was developed by incorporating a high-fat diet and streptozotocin injection. Further, the DE model was screened via the Morris Water Maze test. Primary hippocampal neurons and HT-22 cells were used for in vitro analysis. We found that hyperglycemia exacerbates cognitive impairment in T2DM rats. When we isolated the primary hippocampus neurons, the expression of miR-132 RNA was low in both the DE hippocampus and primary neurons. GSK-3β and Tau 404 were highly expressed in injured HT-22 cells and diabetic hippocampal tissues. miR-132 downregulated the expression of GSK-3β. Besides, a binding and colocalized relationship between GSK3β and Tau was also reported. These findings suggest that miR-132 exerts protective effects from DE injury by repressing GSK-3β expression and alleviating Tau hyperphosphorylation in HT-22 cells and hippocampus tissues. |
format | Online Article Text |
id | pubmed-7906212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-79062122021-03-04 Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway Shi, Li Zhang, Rui Li, Tian Han, Xue Yuan, Nannan Jiang, Lei Zhou, Huimin Xu, Shunjiang Aging (Albany NY) Research Paper Diabetic encephalopathy (DE) is a global concern and Gordian knot worldwide. miRNA-132 (miR-132) is a class of negative gene regulators that promote diabetic pathologic mechanisms and its complications. However, the molecular mechanisms of miR-132 in DE are elusive, thus an alternative therapeutic strategy is urgently in demand. The present study explored the protective effect and the underlying mechanism of miR-132 on DE via the GSK-β/Tau signaling pathway. Experimentally, a type 2 DM rat model was developed by incorporating a high-fat diet and streptozotocin injection. Further, the DE model was screened via the Morris Water Maze test. Primary hippocampal neurons and HT-22 cells were used for in vitro analysis. We found that hyperglycemia exacerbates cognitive impairment in T2DM rats. When we isolated the primary hippocampus neurons, the expression of miR-132 RNA was low in both the DE hippocampus and primary neurons. GSK-3β and Tau 404 were highly expressed in injured HT-22 cells and diabetic hippocampal tissues. miR-132 downregulated the expression of GSK-3β. Besides, a binding and colocalized relationship between GSK3β and Tau was also reported. These findings suggest that miR-132 exerts protective effects from DE injury by repressing GSK-3β expression and alleviating Tau hyperphosphorylation in HT-22 cells and hippocampus tissues. Impact Journals 2020-12-27 /pmc/articles/PMC7906212/ /pubmed/33406505 http://dx.doi.org/10.18632/aging.202418 Text en Copyright: © 2020 Shi et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Shi, Li Zhang, Rui Li, Tian Han, Xue Yuan, Nannan Jiang, Lei Zhou, Huimin Xu, Shunjiang Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway |
title | Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway |
title_full | Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway |
title_fullStr | Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway |
title_full_unstemmed | Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway |
title_short | Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway |
title_sort | decreased mir-132 plays a crucial role in diabetic encephalopathy by regulating the gsk-3β/tau pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906212/ https://www.ncbi.nlm.nih.gov/pubmed/33406505 http://dx.doi.org/10.18632/aging.202418 |
work_keys_str_mv | AT shili decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT zhangrui decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT litian decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT hanxue decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT yuannannan decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT jianglei decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT zhouhuimin decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway AT xushunjiang decreasedmir132playsacrucialroleindiabeticencephalopathybyregulatingthegsk3btaupathway |