Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway

Lee, Yee Ki; Ng, Kwong Man; Lai, Wing Hon; Man, Cornelia; Lieu, Deborah K.; Lau, Chu Pak; Tse, Hung Fat; Siu, Chung Wah

doi:10.1038/aps.2010.188

Cited by 17 publications

(16 citation statements)

References 39 publications

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“…In our system, puerarin treatment harvested about 7% more α-actinin-positive CMs derived from D3 murine ES cells at day 12 of differentiation compared with control group. Comparable with our report, Yee-Ki Lee et al found that ouabain facilitates cardiac differentiation with a 7% increase in the percentage of cardiac troponin I (cTnl)-positve CMs derived from D3 murine ES cells at day 9 of differentiation [9]. However, Wiese et al reported that suramin has no effect on the percentage of cTnI-positive CMs derived from R1 murine ES cells at day 9 of differentiation, but increases the number of cTnI-positive CMs by 5.6 fold at day 22 [10].…”

Section: Discussionsupporting

confidence: 87%

“…So far, proteins from TGFβ, BMP, and Wnt families [4,5,6], cytokines [7], natural or synthetic chemical compounds [3,8,9,10,11]; and several transgenic ES cell systems [12] have been applied to selectively enhance the efficiency of cardiac differentiation from ES cells. Among these reports, retinoic acid and transgenic ES cell system are highlighted by their effects on ventricular specialization of ES cells.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Puerarin on Cardiac Differentiation and Ventricular Specialization of Murine Embryonic Stem Cells

Cheng

Wang

Tang

et al. 2013

Cell Physiol Biochem

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Aims: It is important to screen and identify chemical compounds to improve the efficiency of cardiac differentiation and specialization of embryonic stem (ES) cells. The objective of this study was to investigate the effect of puerarin, a natural phytoestrogen, on the in vitro cardiac differentiation and ventricular specialization of murine ES cells. Methods: Cardiac differentiation of murine ES cells was performed by embryoid body (EB)-based differentiation method. Quantitative RT-PCR, flow cytometry and immunofluorescence were employed to identify cardiomyocytes (CMs) derived from murine ES cells (mES-CMs). Patch clamp was used to study the electrophysiological properties of CMs. Results: We found that continuous puerarin treatment significantly increased the population of ES-CMs which express typical cardiac markers and are electrophysiological intact. Puerarin treatment shifted the cardiac phenotype from pacemaker-like cells to ventricular-like cells, which were Mlc2v-positive and present typical ventricular-like AP. Puerarin up-regulated transcripts involved in cardiac differentiation and ventricular specialization of ES cells. Conclusion: Our results suggest that puerarin promotes cardiac differentiation, and significantly enhances the specialization of mES cells into ventricular-like CMs. Puerarin may be used to increase the yield of ventricular mES-CMs during in vitro differentiation.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Effects of Puerarin on Cardiac Differentiation and Ventricular Specialization of Murine Embryonic Stem Cells

Cheng

Wang

Tang

et al. 2013

Cell Physiol Biochem

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“…It is well known that the ERK1/2 and NF-κB signaling pathways play a pivotal role in many cellular processes, such as proliferation, apoptosis, and differentiation [24][25][26][27] . PAR2 activation induced by the TF/factor VIIa complex can trigger cell signal transduction through different pathways, including ERK1/2 and NF-κB [15,28] .…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate inhibits proliferation and migration of human colon cancer SW620 cells in vitro

Zhou

Wang

et al. 2011

Acta Pharmacol Sin

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Aim: Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent in green tea. The aim of this study is to investigate the effects of EGCG on proliferation and migration of the human colon cancer SW620 cells. Methods: Proliferation and migration of SW620 cells were induced by the protease-activated receptor 2-agonist peptide (PAR2-AP, 100 μmol/L) or factor VIIa (10 nmol/L), and analyzed using MTT and Transwell assays, respectively. The cellular cytoskeleton was stained with rhodamine-conjugated phalloidin and examined with a laser scanning confocal fluorescence microscope. The expression of caspase-7, tissue factor (TF) and matrix metalloproteinase (MMP)-9 in the cells was examined using QT-PCR, ELISA and Western blot assays. The activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor-kappa B (NF-κB) signaling pathways was analyzed with Western blot. Results: Both PAR2-AP and factor VIIa promoted SW620 cell proliferation and migration, and caused cytoskeleton reorganization (increased filopodia and pseudopodia). Pretreatment with EGCG (25, 50, 75, and 100 μg/mL) dose-dependently blocked the cell proliferation and migration induced by PAR2-AP or factor VIIa. EGCG (100 μg/mL) prevented the cytoskeleton changes induced by PAR2-AP or factor VIIa. EGCG (100 μg/mL) counteracted the down-regulation of caspase-7 expression and up-regulation of TF and MMP-9 expression in the cells treated with PAR2-AP or factor VIIa. Furthermore, it blocked the activation of ERK1/2 and NF-κB (p65/RelA) induced by PAR2-AP or factor VIIa. Conclusion: EGCG blocks the proliferation and migration of SW620 cells induced by PAR2-AP and factor VIIa via inhibition of the ERK1/2 and NF-κB pathways. The compound may serve as a preventive and therapeutic agent for colon cancers.

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“…Since cardiotonic steroids (CTS) have been reported to regulate ESC differentiation through Na/K-ATPase-related signaling pathways (Lee et al, 2011), we reasoned that CTS may also affect the differentiation of adult stem cells such as, BMSCs. The above mentioned P3 BMSCs were used to test whether MBG, a specific ligand of Na/K-ATPase, regulates BMSCs differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…Previous reports demonstrated Na/K-ATPase expression in undifferentiated embryonic stem cells (ESCs) as well as in ESC-derived cardiomyocytes (Otsu et al, 2005). CTS such as ouabain promote differentiation of ESCs into cardiac myocytes through an extracellular regulated kinase (ERK) signaling pathway (Lee et al, 2011). This study evaluated whether CTS-induced Na/K-ATPase signaling regulates differentiation in BMSCs.…”

Section: Introductionmentioning

confidence: 99%

Effects of Na/K-ATPase and its ligands on bone marrow stromal cell differentiation

et al. 2014

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Endogenous ligands of Na/K-ATPase have been demonstrated to increase in kidney dysfunction and heart failure. It is also reported that Na/K-ATPase signaling function effects stem cell differentiation. This study evaluated whether Na/K-ATPase activation through its ligands and associated signaling functions affect bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) differentiation capacity. BMSCs were isolated from male Sprague-Dawley rats and cultured in minimal essential medium alpha (MEM-α) supplemented with 15% Fetal Bovine serum (FBS). The results showed that marinobufagenin (MBG), a specific Na/K-ATPase ligand, potentiated rosiglitazone-induced adipogenesis in these BMSCs. Meanwhile, it attenuated BMSCs osteogenesis. Mechanistically, MBG increased CCAAT/enhancer binding protein alpha (C/EBPα) protein expression through activation of an extracellular regulated kinase (ERK) signaling pathway, which leads to enhanced rosiglitazone-induced adipogenesis. Inhibition of ERK activation by U0126 blocks the effect of MBG on C/EBPα expression and on rosiglitazone-induced adipogenesis. Reciprocally, MBG reduced runt-related transcription factor 2 (RunX2) expression, which resulted in the inhibition of osteogenesis induced by β-glycerophosphate/ascorbic acid. MBG also potentiated rosiglitazone-induced adipogenesis in 3T3-L1 cells and in mouse BMSCs. These results suggest that Na/K-ATPase and its signaling functions are involved in the regulation of BMSCs differentiation.

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Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway

Cited by 17 publications

References 39 publications

Effects of Puerarin on Cardiac Differentiation and Ventricular Specialization of Murine Embryonic Stem Cells

Effects of Puerarin on Cardiac Differentiation and Ventricular Specialization of Murine Embryonic Stem Cells

Epigallocatechin-3-gallate inhibits proliferation and migration of human colon cancer SW620 cells in vitro

Effects of Na/K-ATPase and its ligands on bone marrow stromal cell differentiation

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