HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway
Stem cell transplantation is a promising therapy for traumatic brain injury (TBI), but low efficiency of survival and differentiation of transplanted stem cells limits its clinical application. Histone deacetylase 1 (HDAC1) plays important roles in self-renewal of stem cells as well as the recovery...
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doaj-b917463c3d07485e9e91293c1e4cee6a2020-11-25T02:23:44ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-01-011210.3389/fncel.2018.00498426917HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT PathwayLing Xu0Ling Xu1Qu Xing2Tuanjie Huang3Jiankang Zhou4Tengfei Liu5Yuanbo Cui6Yuanbo Cui7Tian Cheng8Yaping Wang9Xinkui Zhou10Bo Yang11Greta Luyuan Yang12Jiewen Zhang13Xingxing Zang14Shanshan Ma15Fangxia Guan16Fangxia Guan17Fangxia Guan18School of Life Sciences, Zhengzhou University, Zhengzhou, ChinaHenan Provincial People’s Hospital, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaTranslational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, ChinaThe First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaThe First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaStuyvesant High School, New York, NY, United StatesHenan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Microbiology and Immunology, Einstein College of Medicine, Bronx, NY, United StatesSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaHenan Provincial People’s Hospital, Zhengzhou, ChinaThe First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaStem cell transplantation is a promising therapy for traumatic brain injury (TBI), but low efficiency of survival and differentiation of transplanted stem cells limits its clinical application. Histone deacetylase 1 (HDAC1) plays important roles in self-renewal of stem cells as well as the recovery of brain disorders. However, little is known about the effects of HDAC1 on the survival and efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in vivo. In this study, our results showed that HDAC1 silence promoted hUC-MSCs engraftment in the hippocampus and increased the neuroprotective effects of hUC-MSCs in TBI mouse model, which was accompanied by improved neurological function, enhanced neurogenesis, decreased neural apoptosis, and reduced oxidative stress in the hippocampus. Further mechanistic studies revealed that the expressions of phosphorylated PTEN (p-PTEN), phosphorylated Akt (p-Akt), and phosphorylated GSK-3β (p-GSK-3β) were upregulated. Intriguingly, the neuroprotective effects of hUC-MSCs with HDAC1 silence on behavioral performance of TBI mice was markedly attenuated by LY294002, an inhibitor of the PI3K/AKT pathway. Taken together, our findings suggest that hUC-MSCs transplantation with HDAC1 silence may provide a potential strategy for treating TBI in the future.https://www.frontiersin.org/article/10.3389/fncel.2018.00498/fullhistone deacetylase 1human umbilical cord derived mesenchymal stem cellstraumatic brain injuryneuroprotectionPI3K/AKT |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ling Xu Ling Xu Qu Xing Tuanjie Huang Jiankang Zhou Tengfei Liu Yuanbo Cui Yuanbo Cui Tian Cheng Yaping Wang Xinkui Zhou Bo Yang Greta Luyuan Yang Jiewen Zhang Xingxing Zang Shanshan Ma Fangxia Guan Fangxia Guan Fangxia Guan |
spellingShingle |
Ling Xu Ling Xu Qu Xing Tuanjie Huang Jiankang Zhou Tengfei Liu Yuanbo Cui Yuanbo Cui Tian Cheng Yaping Wang Xinkui Zhou Bo Yang Greta Luyuan Yang Jiewen Zhang Xingxing Zang Shanshan Ma Fangxia Guan Fangxia Guan Fangxia Guan HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway Frontiers in Cellular Neuroscience histone deacetylase 1 human umbilical cord derived mesenchymal stem cells traumatic brain injury neuroprotection PI3K/AKT |
author_facet |
Ling Xu Ling Xu Qu Xing Tuanjie Huang Jiankang Zhou Tengfei Liu Yuanbo Cui Yuanbo Cui Tian Cheng Yaping Wang Xinkui Zhou Bo Yang Greta Luyuan Yang Jiewen Zhang Xingxing Zang Shanshan Ma Fangxia Guan Fangxia Guan Fangxia Guan |
author_sort |
Ling Xu |
title |
HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway |
title_short |
HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway |
title_full |
HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway |
title_fullStr |
HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway |
title_full_unstemmed |
HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway |
title_sort |
hdac1 silence promotes neuroprotective effects of human umbilical cord-derived mesenchymal stem cells in a mouse model of traumatic brain injury via pi3k/akt pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2019-01-01 |
description |
Stem cell transplantation is a promising therapy for traumatic brain injury (TBI), but low efficiency of survival and differentiation of transplanted stem cells limits its clinical application. Histone deacetylase 1 (HDAC1) plays important roles in self-renewal of stem cells as well as the recovery of brain disorders. However, little is known about the effects of HDAC1 on the survival and efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in vivo. In this study, our results showed that HDAC1 silence promoted hUC-MSCs engraftment in the hippocampus and increased the neuroprotective effects of hUC-MSCs in TBI mouse model, which was accompanied by improved neurological function, enhanced neurogenesis, decreased neural apoptosis, and reduced oxidative stress in the hippocampus. Further mechanistic studies revealed that the expressions of phosphorylated PTEN (p-PTEN), phosphorylated Akt (p-Akt), and phosphorylated GSK-3β (p-GSK-3β) were upregulated. Intriguingly, the neuroprotective effects of hUC-MSCs with HDAC1 silence on behavioral performance of TBI mice was markedly attenuated by LY294002, an inhibitor of the PI3K/AKT pathway. Taken together, our findings suggest that hUC-MSCs transplantation with HDAC1 silence may provide a potential strategy for treating TBI in the future. |
topic |
histone deacetylase 1 human umbilical cord derived mesenchymal stem cells traumatic brain injury neuroprotection PI3K/AKT |
url |
https://www.frontiersin.org/article/10.3389/fncel.2018.00498/full |
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