γ-secretase inhibitor induces adipogenesis of adipose-derived stem cells by regulation of Notch and PPAR-γ

被引：63

作者：

Huang, Y. ^{[2
,3
]}

Yang, X. ^{[2
]}

Wu, Y. ^{[2
]}

Jing, W. ^{[2
]}

Cai, X. ^{[2
]}

Tang, W. ^{[2
]}

Liu, L. ^{[2
]}

Liu, Y. ^{[2
]}

Grottkau, B. E. ^{[1
]}

Lin, Y. ^{[1
,2
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Children & Pediat Orthopaed L, Boston, MA USA

[2] Sichuan Univ, State Key Lab Oral Dis, W China Coll Stomatol, Chengdu 610064, Peoples R China

[3] Capital Med Univ, Beijing Friendship Hosp, Dept Oral & Maxillofacial Surg, Beijing, Peoples R China

来源：

CELL PROLIFERATION | 2010年 / 43卷 / 02期

基金：

中国国家自然科学基金;

关键词：

ACTIVATED-RECEPTOR-GAMMA; SIGNALING PATHWAY; TRANSCRIPTION FACTOR; DIFFERENTIATION; EXPRESSION; PREF-1; PROLIFERATION; PREADIPOCYTES; SPECIFICATION; TARGET;

D O I：

10.1111/j.1365-2184.2009.00661.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Objective: To determine the inhibitory effect and mechanism of Notch signalling on adipogenesis of mouse adipose-derived stem cells (mASCs). Materials and methods: Varied concentrations of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT) were added to mASCs 3 days before adipogenic induction with insulin-containing differentiation medium. The process of adipogenesis and ability of lipid droplet accumulation were analysed using oil red-O staining. The Notch signalling pathway (Notch-1, -2, -3, -4, Hes-1 and Hey-1) and adipogenesis-related factors (PPAR-gamma, DLK-1/Pref-1 and Acrp) were tested using real-time PCR, Western blot analysis and immunofluorescence staining assays. Results: We demonstrated that Notch-2-Hes-1 signalling pathway was inhibited dose-dependently by DAPT in mASCs. In addition, transcription of PPAR-gamma was promoted by DAPT before adipogenic induction, while inhibitor of adipogenesis DLK-1/Pref-1 was further depressed. At early stages of differentiation (2-4 days), adipogenesis in mASCs was advanced and significantly enhanced in 5 and 10 mu m DAPT pre-treated cases. On day 4, in differentiated mASCs cases with DAPT pre-treatment, we also found promotion of activation of de-PPAR-gamma and depression of HES-1, DLK-1/Pref-1 mRNA and protein expression. Conclusions: We conclude that blocking Notch signalling with DAPT enhances adipogenesis of differentiated mASCs at an early stage. It may be due to depression of DLK-1/Pref-1 and promotion of de-PPAR-gamma activation, which work through inhibition of Notch-2-Hes-1 pathway by DAPT.

引用

页码：147 / 156

页数：10

共 49 条

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