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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2023-07-01
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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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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