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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
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.
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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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