Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-β-dependent mechanism

Jeon, Eun-Ju; Moon, Hyun Jung; Lee, Mi‐Jeong; Song, Hae Young; Kim, Young Mi; Bae, Yong Chan; Jung, Jin Sup; Kim, Jae Ho

doi:10.1242/jcs.03281

Cited by 154 publications

(159 citation statements)

References 70 publications

(86 reference statements)

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“…Finally, Jeon et al 41 have shown that siRNA-mediated depletion of SRF and/or myocardin abolished SMC differentiation from mesenchymal stem cell because of failure to form SRF/myocardin complex. Therefore we believe Nrf3 mediated upregulation of myocardin may play a crucial role in SMC differentiation from ESCs.…”

Section: Discussionmentioning

confidence: 99%

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

Pepe

Xiao²,

Zampetaki³

et al. 2010

Circulation Research

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Rationale: Nuclear factor erythroid 2-related factor (Nrf)3, a member of the cap 'N' collar family of transcription factors that bind to the DNA-antioxidant responsive elements, is involved in reactive oxygen species balancing and in muscle precursor migration during early embryo development. Objective: To investigate the functional role of Nrf3 in smooth muscle cell (SMC) differentiation in vitro and in vivo. Methods and Results: Nrf3 was upregulated significantly following 1 to 8 days of SMC differentiation. Knockdown of Nrf3 resulted in downregulation of smooth muscle specific markers expression, whereas enforced expression of Nrf3 enhanced SMC differentiation in a dose-dependent manner. SMC-specific transcription factor myocardin, but not serum response factor, was significantly upregulated by Nrf3 overexpression. Strikingly, the binding of SRF and myocardin to the promoter of smooth muscle differentiation genes was dramatically increased by Nrf3 overexpression, and Nrf3 can directly bind to the promoters of SMC differentiation genes as demonstrated by chromatin immunoprecipitation assay. Moreover, NADPH-derived reactive oxygen species production during SMC differentiation was further enhanced by Nrf3 overexpression through upregulation of NADPH oxidase and inhibition of antioxidant signaling pathway. In addition, Nrf3 was involved in the endoplasmic reticulum stressor induced SMC differentiation. (SMCs). [1][2][3] Our previous studies showed that growth factor stimulation, 2 mechanical force or extracellular matrix 4 can be used to drive ESC differentiation toward the vascular lineage. We have established an in vitro model for ESC differentiation into SMCs, 3 which involves the choice of extracellular matrix protein collagen IV, 3,5,6 to investigate SMC differentiation more closely. In the adult organism, SMCs have the main physiological function of contracting and controlling the blood vessel tone, diameter, blood pressure and blood flow. In response to vascular injury, SMCs dramatically increase their rate of proliferation, migration and synthetic capacity. 7,8 Atherosclerosis and postangioplasty restenosis, for example, are characterized by the development of an enlarged neointima. 9 The cells responsible for the neointima formation have been identified as not only SMC migrating from the tunica media, 10 but also vascular progenitors that originate from the circulation and the perivascular adventitia, which differentiate into vascular SMCs in the lesion. 11-14 However, the mechanisms involved in SMC differentiation in vitro and in vivo is still poorly understood.In a microarray screen for factors involved in vascular progenitor differentiation, we identified nuclear factor erythroid 2-related factor (Nrf)3 expression to be constantly modulated. Nrf3 is the most recently identified member of the Nrf family and contains a domain homologous to the cap 'N' collar (CNC) transcription factors. 15 The CNC domain is a unique, conserved region, located at the amino-terminus of the bZIP domain. 16 Nrf3 heterodim...

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Section: Discussionmentioning

confidence: 99%

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

Pepe

Xiao²,

Zampetaki³

et al. 2010

Circulation Research

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“…A similar approach has previously been used to induce differentiation of MSCs into smooth muscle-like cells when cultured on 2D tissue culture surfaces. 34,35 Differentiation following TGF-b1 binding results in signaling through the Smad pathway, causing inhibition of cell FIG. 3.…”

Section: Discussionmentioning

confidence: 99%

“…Color images available online at www.liebertpub.com/tec proliferation and induction of contractile proteins in smooth muscle cells. [34][35][36] Incubation of the TIPS microcarriers in the differentiation medium resulted in the induced expression of the three myogenic markers-caldesmon, calponin, and myosin heavy chains. These markers are intermediate to late markers of smooth muscle cell differentiation, unlike a-smooth muscle actin, which is considered to be an early marker of smooth muscle differentiation and, importantly, is not limited only to expression in smooth muscle cells.…”

Section: Figmentioning

confidence: 99%

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

Parmar

Ahmadi²,

Day³

2015

Tissue Engineering Part C: Methods

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Muscle degeneration is a prevalent disease, particularly in aging societies where it has a huge impact on quality of life and incurs colossal health costs. Suitable donor sources of smooth muscle cells are limited and minimally invasive therapeutic approaches are sought that will augment muscle volume by delivering cells to damaged or degenerated areas of muscle. For the first time, we report the use of highly porous microcarriers produced using thermally induced phase separation (TIPS) to expand and differentiate adipose-derived mesenchymal stem cells (AdMSCs) into smooth muscle-like cells in a format that requires minimal manipulation before clinical delivery. AdMSCs readily attached to the surface of TIPS microcarriers and proliferated while maintained in suspension culture for 12 days. Switching the incubation medium to a differentiation medium containing 2 ng/ mL transforming growth factor beta-1 resulted in a significant increase in both the mRNA and protein expression of cell contractile apparatus components caldesmon, calponin, and myosin heavy chains, indicative of a smooth muscle cell-like phenotype. Growth of smooth muscle cells on the surface of the microcarriers caused no change to the integrity of the polymer microspheres making them suitable for a cell-delivery vehicle. Our results indicate that TIPS microspheres provide an ideal substrate for the expansion and differentiation of AdMSCs into smooth muscle-like cells as well as a microcarrier delivery vehicle for the attached cells ready for therapeutic applications.

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“…As one important type of adult stem cells, mesenchymal stem cells (MSCs) can be highly expanded in vitro and differentiate into a variety of cell types, such as osteoblasts, adipocytes, myocytes, and so on (1,2). It has been demonstrated that MSCs can differentiate into smooth muscle cells (SMCs) in response to transforming growth factor-b (TGF-b) (3), sphingosylphosphorylcholine (SPC) (4) and directly contact with vascular endothelial cells (5). In vivo, MSCs transplanted into the heart can differentiate into SMCs and contribute to the remodeling of vasculature (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Members of the TGF-b family of cytokines increase the expression levels of SMC-specific genes including a-smooth muscle actin (a-SMA) in a variety of cell types, including human adipose-tissue-derived MSCs (3,4,11,12). TGF-b coordinately upregulates a variety of SMC-specific genes including smooth muscle myosin heavy chain (SMMHC), smooth muscle 22 alpha (SM22a), and a-SMA in cultured SMCs derived from mature blood vessels (11).…”

Section: Introductionmentioning

confidence: 99%

Cooperation of myocardin and smad2 in inducing differentiation of mesenchymal stem cells into smooth muscle cells

et al. 2012

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SummarySeveral reports demonstrated that mesenchymal stem cells (MSCs) might differentiate into smooth muscle cells (SMCs) in vitro and in vivo. It has been shown that myocardin protein is a strong inducer of smooth muscle genes and MSCs can differentiate into SMCs in response to transforming growth factor-b (TGF-b). However, the relationship or link between myocardin and TGF-b3-induced MSC differentiation has not been fully elucidated. Here, we demonstrated that both myocardin and TGF-b3 were able to induce differentiation of rat bone marrow-derived MSCs toward smooth-muscle-like cell types, as evidenced by increasing expression of SMC-specific genes. Of note, myocardin cooperated with Smad2 to synergistically activate SM22a promoter and significantly enhance the expression of SM22a. Report assays with site-direct mutation analysis of SM22a promoter demonstrated that myocardin and Smad2 coactivated SM22a promoter mainly depending on CArG box and less on smad binding elements (SBE) sites as well. These findings reveal the cooperation of myocardin and Smad2 in process of MSC differentiation into SMCs.2012 IUBMB IUBMB Life, 64(4): [331][332][333][334][335][336][337][338][339] 2012

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Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-β-dependent mechanism

Cited by 154 publications

References 70 publications

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

Cooperation of myocardin and smad2 in inducing differentiation of mesenchymal stem cells into smooth muscle cells

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