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Ghrelin promotes neural differentiation of adipose tissue-derived mesenchymal stem cell via AKT/mTOR and ß-catenin signaling pathways.
Liu, Gui-Bo; Pan, Yan-Ming; Liu, Yun-Shuang; Hu, Jia-Hang; Zhang, Xiao-Dong; Zhang, Da-Wei; Wang, Ying; Feng, Yu-Kuan; Yu, Jian-Bo; Cheng, Yong-Xia.
Afiliação
  • Liu GB; Department of Anatomy, School of Basic Medical Sciences, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Pan YM; Institute of Neural Tissue Engineering, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Liu YS; Department of Anatomy, School of Basic Medical Sciences, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Hu JH; Key Laboratory of Cancer Prevention and Treatment of Heilongjiang Province, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Zhang XD; Department of Medical Imaging, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Zhang DW; Department of Medical Imaging, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Wang Y; Department of Infectious Diseases, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Feng YK; Department of Anatomy, School of Basic Medical Sciences, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Yu JB; Department of Anatomy, School of Basic Medical Sciences, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
  • Cheng YX; Institute of Neural Tissue Engineering, Mudanjiang Medical College, Mudanjiang, People's Republic of China.
Kaohsiung J Med Sci ; 36(6): 405-416, 2020 Jun.
Article em En | MEDLINE | ID: mdl-32003536
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 ß-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 ß-catenin, p-GSK-3ß, p-AKT, and p-mTOR was increased by ghrelin, indicating an activation of ß-catenin and AKT/mTOR signaling after the ghrelin treatment. Importantly, inhibition of ß-catenin or AKT/mTOR signaling suppressed ghrelin-induced neurogenesis. Therefore, we demonstrate that ghrelin promotes neural differentiation of ADSCs through the activation of ß-catenin and AKT/mTOR signaling pathways.
Assuntos
Adipócitos/efeitos dos fármacos; Grelina/farmacologia; Células-Tronco Mesenquimais/efeitos dos fármacos; Neurônios/efeitos dos fármacos; Proteínas Proto-Oncogênicas c-akt/genética; Serina-Treonina Quinases TOR/genética; beta Catenina/genética; Adipócitos/citologia; Adipócitos/metabolismo; Tecido Adiposo/citologia; Tecido Adiposo/metabolismo; Animais; Anticorpos Heterófilos/farmacologia; Diferenciação Celular/efeitos dos fármacos; Regulação da Expressão Gênica; Grelina/genética; Grelina/metabolismo; Proteína Glial Fibrilar Ácida/genética; Proteína Glial Fibrilar Ácida/metabolismo; Glicogênio Sintase Quinase 3 beta/genética; Glicogênio Sintase Quinase 3 beta/metabolismo; Compostos Heterocíclicos com 3 Anéis/farmacologia; Receptores de Hialuronatos/genética; Receptores de Hialuronatos/metabolismo; Integrina beta1/genética; Integrina beta1/metabolismo; Masculino; Células-Tronco Mesenquimais/citologia; Células-Tronco Mesenquimais/metabolismo; Proteínas Associadas aos Microtúbulos/genética; Proteínas Associadas aos Microtúbulos/metabolismo; Nestina/genética; Nestina/metabolismo; Neurônios/citologia; Neurônios/metabolismo; Cultura Primária de Células; Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores; Proteínas Proto-Oncogênicas c-akt/metabolismo; Ratos; Ratos Sprague-Dawley; Transdução de Sinais; Serina-Treonina Quinases TOR/metabolismo; Antígenos Thy-1/genética; Antígenos Thy-1/metabolismo; Tubulina (Proteína)/genética; Tubulina (Proteína)/metabolismo; beta Catenina/antagonistas & inibidores; beta Catenina/metabolismo
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adipócitos / Proteínas Proto-Oncogênicas c-akt / Beta Catenina / Grelina / Serina-Treonina Quinases TOR / Células-Tronco Mesenquimais / Neurônios Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adipócitos / Proteínas Proto-Oncogênicas c-akt / Beta Catenina / Grelina / Serina-Treonina Quinases TOR / Células-Tronco Mesenquimais / Neurônios Idioma: En Ano de publicação: 2020 Tipo de documento: Article