Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways

Abstract Adipose tissue‐derived mesenchymal stem cells (ADSCs) are multipotent cells that can differentiate into various cell types. This study aimed to investigate the effect of ghrelin on the neural differentiation of rat ADSCs and underlying molecular mechanisms. Rat ADSCs were isolated and third...

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Main Authors: Gui‐Bo Liu, Yan‐Ming Pan, Yun‐Shuang Liu, Jia‐Hang Hu, Xiao‐Dong Zhang, Da‐Wei Zhang, Ying Wang, Yu‐Kuan Feng, Jian‐Bo Yu, Yong‐Xia Cheng
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:Kaohsiung Journal of Medical Sciences
Subjects:
Online Access:https://doi.org/10.1002/kjm2.12188
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author Gui‐Bo Liu
Yan‐Ming Pan
Yun‐Shuang Liu
Jia‐Hang Hu
Xiao‐Dong Zhang
Da‐Wei Zhang
Ying Wang
Yu‐Kuan Feng
Jian‐Bo Yu
Yong‐Xia Cheng
author_facet Gui‐Bo Liu
Yan‐Ming Pan
Yun‐Shuang Liu
Jia‐Hang Hu
Xiao‐Dong Zhang
Da‐Wei Zhang
Ying Wang
Yu‐Kuan Feng
Jian‐Bo Yu
Yong‐Xia Cheng
author_sort Gui‐Bo Liu
collection DOAJ
description Abstract Adipose tissue‐derived mesenchymal stem cells (ADSCs) are multipotent cells that can differentiate into various cell types. This study aimed to investigate the effect of ghrelin on the neural differentiation of rat ADSCs and underlying molecular mechanisms. Rat ADSCs were isolated and third‐passage ADSCs were used in this study. The isolated ADSCs were characterized by flow cytometry analysis for MSCs' surface expression markers as evidenced by positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD11b/2f/c. The multilineage differentiation of ADSCs was confirmed by adipogenic, osteogenic, and neural differentiation. After induction of neurogenesis, the differentiated cells were identified by development of neuron‐like morphology and expression of neural markers including glial fibrillary acidic protein, Nestin, MAP2, and β‐Tubulin III using immunofluorescence and western blot. Ghrelin concentration dependently elevated the proportion of neural‐like cells and branching dendrites, as well as upregulated the expression of neural markers. Further, the expression of nuclear β‐catenin, p‐GSK‐3β, p‐AKT, and p‐mTOR was increased by ghrelin, indicating an activation of β‐catenin and AKT/mTOR signaling after the ghrelin treatment. Importantly, inhibition of β‐catenin or AKT/mTOR signaling suppressed ghrelin‐induced neurogenesis. Therefore, we demonstrate that ghrelin promotes neural differentiation of ADSCs through the activation of β‐catenin and AKT/mTOR signaling pathways.
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spelling doaj.art-762ba6a52bfb456a8b1da656a0ef1a7b2022-12-21T21:34:02ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502020-06-0136640541610.1002/kjm2.12188Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathwaysGui‐Bo Liu0Yan‐Ming Pan1Yun‐Shuang Liu2Jia‐Hang Hu3Xiao‐Dong Zhang4Da‐Wei Zhang5Ying Wang6Yu‐Kuan Feng7Jian‐Bo Yu8Yong‐Xia Cheng9Department of Anatomy, School of Basic Medical Sciences Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Anatomy, School of Basic Medical Sciences Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Medical Imaging Hongqi Hospital of Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Medical Imaging Hongqi Hospital of Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Infectious Diseases Hongqi Hospital of Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Anatomy, School of Basic Medical Sciences Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Anatomy, School of Basic Medical Sciences Mudanjiang Medical College Mudanjiang People's Republic of ChinaDepartment of Anatomy, School of Basic Medical Sciences Mudanjiang Medical College Mudanjiang People's Republic of ChinaKey Laboratory of Cancer Prevention and Treatment of Heilongjiang Province Mudanjiang Medical College Mudanjiang People's Republic of ChinaKey Laboratory of Cancer Prevention and Treatment of Heilongjiang Province Mudanjiang Medical College Mudanjiang People's Republic of ChinaAbstract Adipose tissue‐derived mesenchymal stem cells (ADSCs) are multipotent cells that can differentiate into various cell types. This study aimed to investigate the effect of ghrelin on the neural differentiation of rat ADSCs and underlying molecular mechanisms. Rat ADSCs were isolated and third‐passage ADSCs were used in this study. The isolated ADSCs were characterized by flow cytometry analysis for MSCs' surface expression markers as evidenced by positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD11b/2f/c. The multilineage differentiation of ADSCs was confirmed by adipogenic, osteogenic, and neural differentiation. After induction of neurogenesis, the differentiated cells were identified by development of neuron‐like morphology and expression of neural markers including glial fibrillary acidic protein, Nestin, MAP2, and β‐Tubulin III using immunofluorescence and western blot. Ghrelin concentration dependently elevated the proportion of neural‐like cells and branching dendrites, as well as upregulated the expression of neural markers. Further, the expression of nuclear β‐catenin, p‐GSK‐3β, p‐AKT, and p‐mTOR was increased by ghrelin, indicating an activation of β‐catenin and AKT/mTOR signaling after the ghrelin treatment. Importantly, inhibition of β‐catenin or AKT/mTOR signaling suppressed ghrelin‐induced neurogenesis. Therefore, we demonstrate that ghrelin promotes neural differentiation of ADSCs through the activation of β‐catenin and AKT/mTOR signaling pathways.https://doi.org/10.1002/kjm2.12188adipose tissue‐derived mesenchymal stem cell (ADSC)AKT/mTORghrelinneural differentiationβ‐catenin
spellingShingle Gui‐Bo Liu
Yan‐Ming Pan
Yun‐Shuang Liu
Jia‐Hang Hu
Xiao‐Dong Zhang
Da‐Wei Zhang
Ying Wang
Yu‐Kuan Feng
Jian‐Bo Yu
Yong‐Xia Cheng
Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways
Kaohsiung Journal of Medical Sciences
adipose tissue‐derived mesenchymal stem cell (ADSC)
AKT/mTOR
ghrelin
neural differentiation
β‐catenin
title Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways
title_full Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways
title_fullStr Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways
title_full_unstemmed Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways
title_short Ghrelin promotes neural differentiation of adipose tissue‐derived mesenchymal stem cell via AKT/mTOR and β‐catenin signaling pathways
title_sort ghrelin promotes neural differentiation of adipose tissue derived mesenchymal stem cell via akt mtor and β catenin signaling pathways
topic adipose tissue‐derived mesenchymal stem cell (ADSC)
AKT/mTOR
ghrelin
neural differentiation
β‐catenin
url https://doi.org/10.1002/kjm2.12188
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