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Inhibition of Notch Signaling Promotes the Adipogenic Differentiation of Mesenchymal Stem Cells Through Autophagy Activation and PTEN-PI3K/AKT/mTOR Pathway.
Song, Bao-quan; Chi, Ying; Li, Xue; Du, Wen-jing; Han, Zhi-Bo; Tian, Jian-jian; Li, Juan-juan; Chen, Fang; Wu, He-he; Han, Li-xin; Lu, Shi-hong; Zheng, Yi-zhou; Han, Zhong-chao.
Afiliación
  • Song BQ; State Key Laboratory of Experimental Hematology, National Engineering Research Center of Stem Cells, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Cell Physiol Biochem ; 36(5): 1991-2002, 2015.
Article en En | MEDLINE | ID: mdl-26202359
BACKGROUND: The Notch signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. This study was designed to determine the role of Notch signaling in adipogenic differentiation of human bone marrow derived MSCs (BM-MSCs). METHODS: The Notch signaling was inhibited by the γ-secretase inhibitor N-[N-(3,5-difluor- ophenacetyl-L-alanyl)]-S-phenylglycine t-butylester (DAPT). The markers involving adipogenic differentiation of MSCs, the relative pathway PTEN-PI3K/Akt/mTOR and autophagy activation were then analyzed. Furthermore, the autophagy inhibitor chloroquine (CQ) and 3-methyladenine (3-MA) were used to study the role of autophagy in the DAPT-induced the adipogenic differentiation of MSCs. RESULTS: We first confirmed the down -regulation of Notch gene expression during MSCs adipocyte differentiation, and showed that the inhibition of Notch signaling significantly enhanced adipogenic differentiation of MSCs. Furthermore, Notch inhibitor DAPT induced early autophagy by acting on PTEN-PI3K/Akt/mTOR pathway. The autophagy inhibitor CQ and 3-MA dramatically abolished the effects of DAPT-induced autophagy and adipogenic differentiation of MSCs. CONCLUSION: Our results indicate that inhibition of Notch signaling could promote MSCs adipogenesis mediated by autophagy involving PTEN-PI3K/Akt/mTOR pathway. Notch signaling could be a novel target for regulating the adipogenic differentiation of MSCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Transducción de Señal / Diferenciación Celular / Tejido Adiposo / Fosfatidilinositol 3-Quinasas / Dipéptidos / Fosfohidrolasa PTEN / Proteínas Proto-Oncogénicas c-akt / Receptores Notch / Serina-Treonina Quinasas TOR Límite: Humans Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Transducción de Señal / Diferenciación Celular / Tejido Adiposo / Fosfatidilinositol 3-Quinasas / Dipéptidos / Fosfohidrolasa PTEN / Proteínas Proto-Oncogénicas c-akt / Receptores Notch / Serina-Treonina Quinasas TOR Límite: Humans Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania