Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells

Yu, Weihua; Chen, Zhenguang; Zhang, Jinli; Zhang, Lirong; Hui, Ke; Hu, Lihua; Peng, Yanwen; Zhang, Xiuming; Shu-nong, LI; Lahn, Bruce T.; Xiang, Andy Peng

doi:10.1007/s11010-007-9661-9

Cited by 112 publications

(81 citation statements)

References 26 publications

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“…It is known that mTOR signaling positively regulates expression of the adipogenic gene PPAR2, which is critical for adipogenesis of BMMSCs (Kim and Chen, 2004;Yu et al, 2008;Zhang et al, 2009). However, controversial findings were reported regarding mTOR signaling in osteogenesis in that mTOR may be required for osteoblast proliferation, which is involved in several signaling pathways through IL6 (Kozawa et al, 2001;Takai et al, 2007;Takai et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

mTOR inhibition rescues osteopenia in mice with systemic sclerosis

Chen¹,

Akiyama²,

Wang³

et al. 2015

J Cell Biol

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Section: Discussionmentioning

confidence: 99%

mTOR inhibition rescues osteopenia in mice with systemic sclerosis

Chen¹,

Akiyama²,

Wang³

et al. 2015

J Cell Biol

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“…mTORC1 promotes PPARc action and adipogenesis Because mTORC1 senses growth factors and nutrients, which are the main factors driving adipose tissue accumulation in mammals, several groups have tested the role of mTORC1 in regulating fat cell formation. mTORC1 inhibition severely impairs adipogenesis and adipose cell maintenance in vitro (Cho et al, 2004;Gagnon et al, 2001;Kim and Chen, 2004;Polak et al, 2008;Yu et al, 2008;Zhang et al, 2009). mTORC1 affects these processes by modulating the expression and the activity of peroxisome proliferatoractivated receptor c (PPARc), a nuclear receptor that controls the expression of genes that are required for fatty acid synthesis, uptake and esterification (reviewed by Rosen and MacDougald, 2006).…”

Section: Mtorc1 Promotes Lipid Biosynthesis Through Srebpsmentioning

confidence: 99%

Regulation of mTORC1 and its impact on gene expression at a glance

Laplante

Sabatini

2013

Journal of Cell Science

543

516

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The mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates key cellular functions linked to the promotion of cell growth and metabolism. This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabolic processes in response to growth factors and nutrients. Of the two mTOR complexes, mTORC1 is by far the best characterized. When active, mTORC1 triggers cell growth and proliferation by promoting protein synthesis, lipid biogenesis, and metabolism, and by reducing autophagy. The fact that mTORC1 deregulation is associated with several human diseases, such as type 2 diabetes, cancer, obesity and neurodegeneration, highlights its importance in the maintenance of cellular homeostasis. Over the last years, several groups observed that mTORC1 inhibition, in addition to reducing protein synthesis, deeply affects gene transcription. Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPARγ, PPARα, HIF1α, YY1–PGC1α and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts.

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“…For example, the levels of components of the PI3K/Akt pathway and its downstream proteins mTOR, FOXO1, p27(kip1), and p70S6K are increased during the differentiation of MSCs into adipocytes. [114][115][116] The inhibition of this pathway with the PI3K-specific inhibitor LY294002 resulted in decreased adipogenesis, indicating that the PI3K/Akt pathway plays an important role in adipogenesis. 114 The activation of the downstream protein mTOR is sufficient to promote adipogenesis, and this process is inhibited by rapamycin.…”

Section: 113mentioning

confidence: 99%

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Chen

Crawford

Chen

et al. 2013

Tissue Engineering Part B: Reviews

204

161

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Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway. MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

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Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells

Cited by 112 publications

References 26 publications

mTOR inhibition rescues osteopenia in mice with systemic sclerosis

mTOR inhibition rescues osteopenia in mice with systemic sclerosis

Regulation of mTORC1 and its impact on gene expression at a glance

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

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