P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model
Abstract Background The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related compon...
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BMC
2023-07-01
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Series: | Cell Communication and Signaling |
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Online Access: | https://doi.org/10.1186/s12964-023-01173-6 |
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author | Xiang-Xin Chen Tao Tao Xun-Zhi Liu Wei Wu Jin-Wei Wang Ting-Ting Yue Xiao-Jian Li Yan Zhou Sen Gao Bin Sheng Zheng Peng Hua-Jie Xu Peng-Fei Ding Ling-Yun Wu Ding-Ding Zhang Yue Lu Chun-Hua Hang Wei Li |
author_facet | Xiang-Xin Chen Tao Tao Xun-Zhi Liu Wei Wu Jin-Wei Wang Ting-Ting Yue Xiao-Jian Li Yan Zhou Sen Gao Bin Sheng Zheng Peng Hua-Jie Xu Peng-Fei Ding Ling-Yun Wu Ding-Ding Zhang Yue Lu Chun-Hua Hang Wei Li |
author_sort | Xiang-Xin Chen |
collection | DOAJ |
description | Abstract Background The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. Methods We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. Results In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. Conclusion P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract |
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language | English |
last_indexed | 2024-03-12T22:14:46Z |
publishDate | 2023-07-01 |
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series | Cell Communication and Signaling |
spelling | doaj.art-42993ade0bfa4573bdf4410daa1e121d2023-07-23T11:20:53ZengBMCCell Communication and Signaling1478-811X2023-07-0121111510.1186/s12964-023-01173-6P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage modelXiang-Xin Chen0Tao Tao1Xun-Zhi Liu2Wei Wu3Jin-Wei Wang4Ting-Ting Yue5Xiao-Jian Li6Yan Zhou7Sen Gao8Bin Sheng9Zheng Peng10Hua-Jie Xu11Peng-Fei Ding12Ling-Yun Wu13Ding-Ding Zhang14Yue Lu15Chun-Hua Hang16Wei Li17Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityInstitute of Neurosurgery, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityInstitute of Neurosurgery, Nanjing UniversityInstitute of Neurosurgery, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityInstitute of Neurosurgery, Nanjing UniversityInstitute of Neurosurgery, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract Background The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. Methods We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. Results In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. Conclusion P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstracthttps://doi.org/10.1186/s12964-023-01173-6DAPK1P38LC3-associated phagocytosisMicrogliaSubarachnoid hemorrhage |
spellingShingle | Xiang-Xin Chen Tao Tao Xun-Zhi Liu Wei Wu Jin-Wei Wang Ting-Ting Yue Xiao-Jian Li Yan Zhou Sen Gao Bin Sheng Zheng Peng Hua-Jie Xu Peng-Fei Ding Ling-Yun Wu Ding-Ding Zhang Yue Lu Chun-Hua Hang Wei Li P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model Cell Communication and Signaling DAPK1 P38 LC3-associated phagocytosis Microglia Subarachnoid hemorrhage |
title | P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model |
title_full | P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model |
title_fullStr | P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model |
title_full_unstemmed | P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model |
title_short | P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model |
title_sort | p38 dapk1 axis regulated lc3 associated phagocytosis lap of microglia in an in vitro subarachnoid hemorrhage model |
topic | DAPK1 P38 LC3-associated phagocytosis Microglia Subarachnoid hemorrhage |
url | https://doi.org/10.1186/s12964-023-01173-6 |
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