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The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy
Prostaglandin D2 (PGD2) is the most abundant prostaglandin in the brain, but its involvement in brain damage caused by type 2 diabetes (T2D) has not been reported. In the present study, we found that increased PGD2 content is related to the inhibition of autophagy, which aggravates brain damage in T...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495389/ https://www.ncbi.nlm.nih.gov/pubmed/34671214 http://dx.doi.org/10.7150/ijbs.60149 |
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author | Yang, Yang Xiang, Pu Chen, Qi Luo, Ying Wang, Hong Li, Huan Yang, Lu Hu, Congli Zhang, Jiahua Li, Yuke Xia, Hui Chen, Zhihao Yang, Junqing |
author_facet | Yang, Yang Xiang, Pu Chen, Qi Luo, Ying Wang, Hong Li, Huan Yang, Lu Hu, Congli Zhang, Jiahua Li, Yuke Xia, Hui Chen, Zhihao Yang, Junqing |
author_sort | Yang, Yang |
collection | PubMed |
description | Prostaglandin D2 (PGD2) is the most abundant prostaglandin in the brain, but its involvement in brain damage caused by type 2 diabetes (T2D) has not been reported. In the present study, we found that increased PGD2 content is related to the inhibition of autophagy, which aggravates brain damage in T2D, and may be involved in the imbalanced expression of the corresponding PGD2 receptors DP1 and DP2. We demonstrated that DP2 inhibited autophagy and promotedT2D-induced brain damage by activating the PI3K/AKT/mTOR pathway, whereas DP1enhanced autophagy and amelioratedT2D brain damage by activating the cAMP/PKA pathway. In a T2D rat model, DP1 expression was decreased, and DP2 expression was increased; therefore, the imbalance in PGD2-DPs may be involved in T2D brain damage through the regulation of autophagy. However, there have been no reports on whether PKA can directly inhibit mTOR. The PKA catalytic subunit (PKA-C) has three subtypes (α, β and γ), and γ is not expressed in the brain. Subsequently, we suggested that PKA could directly interact with mTOR through PKA-C(α) and PKA-C(β). Our results suggest that the imbalance in PGD2-DPs is related to changes in autophagy levels in T2D brain damage, and PGD2 is involved in T2D brain damage by promoting autophagy via DP1-PKA/mTOR and inhibiting autophagy via DP2-PI3K/AKT/mTOR. |
format | Online Article Text |
id | pubmed-8495389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-84953892021-10-19 The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy Yang, Yang Xiang, Pu Chen, Qi Luo, Ying Wang, Hong Li, Huan Yang, Lu Hu, Congli Zhang, Jiahua Li, Yuke Xia, Hui Chen, Zhihao Yang, Junqing Int J Biol Sci Research Paper Prostaglandin D2 (PGD2) is the most abundant prostaglandin in the brain, but its involvement in brain damage caused by type 2 diabetes (T2D) has not been reported. In the present study, we found that increased PGD2 content is related to the inhibition of autophagy, which aggravates brain damage in T2D, and may be involved in the imbalanced expression of the corresponding PGD2 receptors DP1 and DP2. We demonstrated that DP2 inhibited autophagy and promotedT2D-induced brain damage by activating the PI3K/AKT/mTOR pathway, whereas DP1enhanced autophagy and amelioratedT2D brain damage by activating the cAMP/PKA pathway. In a T2D rat model, DP1 expression was decreased, and DP2 expression was increased; therefore, the imbalance in PGD2-DPs may be involved in T2D brain damage through the regulation of autophagy. However, there have been no reports on whether PKA can directly inhibit mTOR. The PKA catalytic subunit (PKA-C) has three subtypes (α, β and γ), and γ is not expressed in the brain. Subsequently, we suggested that PKA could directly interact with mTOR through PKA-C(α) and PKA-C(β). Our results suggest that the imbalance in PGD2-DPs is related to changes in autophagy levels in T2D brain damage, and PGD2 is involved in T2D brain damage by promoting autophagy via DP1-PKA/mTOR and inhibiting autophagy via DP2-PI3K/AKT/mTOR. Ivyspring International Publisher 2021-09-21 /pmc/articles/PMC8495389/ /pubmed/34671214 http://dx.doi.org/10.7150/ijbs.60149 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Yang, Yang Xiang, Pu Chen, Qi Luo, Ying Wang, Hong Li, Huan Yang, Lu Hu, Congli Zhang, Jiahua Li, Yuke Xia, Hui Chen, Zhihao Yang, Junqing The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
title | The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
title_full | The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
title_fullStr | The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
title_full_unstemmed | The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
title_short | The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
title_sort | imbalance of pgd2-dps pathway is involved in the type 2 diabetes brain injury by regulating autophagy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495389/ https://www.ncbi.nlm.nih.gov/pubmed/34671214 http://dx.doi.org/10.7150/ijbs.60149 |
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