Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13287-018-1086-8
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dc.titleWnt/β-catenin-mediated signaling re-activates proliferation of matured cardiomyocytes
dc.contributor.authorFan, Y.
dc.contributor.authorHo, B.X.
dc.contributor.authorPang, J.K.S.
dc.contributor.authorPek, N.M.Q.
dc.contributor.authorHor, J.H.
dc.contributor.authorNg, S.-Y.
dc.contributor.authorSoh, B.-S.
dc.date.accessioned2020-09-07T05:01:31Z
dc.date.available2020-09-07T05:01:31Z
dc.date.issued2018
dc.identifier.citationFan, Y., Ho, B.X., Pang, J.K.S., Pek, N.M.Q., Hor, J.H., Ng, S.-Y., Soh, B.-S. (2018). Wnt/β-catenin-mediated signaling re-activates proliferation of matured cardiomyocytes. Stem Cell Research and Therapy 9 (1) : 338. ScholarBank@NUS Repository. https://doi.org/10.1186/s13287-018-1086-8
dc.identifier.issn17576512
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174516
dc.description.abstractBackground: The Wnt/β-catenin signaling pathway plays an important role in the development of second heart field (SHF Isl1+) that gives rise to the anterior heart field (AHF) cardiac progenitor cells (CPCs) for the formation of the right ventricle, outflow tract (OFT), and a portion of the inflow tract (IFT). During early cardiogenesis, these AHF CPCs reside within the pharyngeal mesoderm (PM) that provides a microenvironment for them to receive signals that direct their cell fates. Here, N-cadherin, which is weakly expressed by CPCs, plays a significant role by promoting the adhesion of CPCs within the AHF, regulating β-catenin levels in the cytoplasm to maintain high Wnt signaling and cardioproliferation while also preventing the premature differentiation of CPCs. On the contrary, strong expression of N-cadherin observed throughout matured myocardium is associated with downregulation of Wnt signaling due to ?-catenin sequestration at the cell membrane, inhibiting cardioproliferation. As such, upregulation of Wnt signaling pathway to enhance cardiac tissue proliferation in mature cardiomyocytes can be explored as an interesting avenue for regenerative treatment to patients who have suffered from myocardial infarction. Methods: To investigate if Wnt signaling is able to enhance cellular proliferation of matured cardiomyocytes, we treated cardiomyocytes isolated from adult mouse heart and both murine and human ES cell-derived matured cardiomyocytes with N-cadherin antibody or CHIR99021 GSK inhibitor in an attempt to increase levels of cytoplasmic β-catenin. Immunostaining, western blot, and quantitative PCR for cell proliferation markers, cell cycling markers, and Wnt signaling pathway markers were used to quantitate re-activation of cardioproliferation and Wnt signaling. Results: N-cadherin antibody treatment releases sequestered β-catenin at N-cadherin-based adherens junction, resulting in an increased pool of cytoplasmic β-catenin, similar in effect to CHIR99021 GSK inhibitor treatment. Both treatments therefore upregulate Wnt signaling successfully and result in significant increases in matured cardiomyocyte proliferation. Conclusion: Although both N-cadherin antibody and CHIR99021 treatment resulted in increased Wnt signaling and cardioproliferation, CHIR99021 was found to be the more effective treatment method for human ES cell-derived cardiomyocytes. Therefore, we propose that CHIR99021 could be a potential therapeutic option for myocardial infarction patients in need of regeneration of cardiac tissue. © 2018 The Author(s).
dc.publisherBioMed Central Ltd.
dc.sourceUnpaywall 20200831
dc.subject6 [[2 [[4 (2,4 dichlorophenyl) 5 (4 methyl 1h imidazol 2 yl) 2 pyrimidinyl]amino]ethyl]amino]nicotinonitrile
dc.subjectbeta catenin
dc.subjectcell marker
dc.subjectnerve cell adhesion molecule
dc.subjectprotein antibody
dc.subjectWnt protein
dc.subjectbeta catenin
dc.subjectcadherin
dc.subjectCdh2 protein, mouse
dc.subjectmessenger RNA
dc.subjectpyridine derivative
dc.subjectpyrimidine derivative
dc.subjectadult
dc.subjectanimal cell
dc.subjectArticle
dc.subjectcardiac muscle cell
dc.subjectcell activation
dc.subjectcell maturation
dc.subjectcell proliferation
dc.subjectcontrolled study
dc.subjectcytoplasm
dc.subjecthuman
dc.subjectimmunohistochemistry
dc.subjectmouse
dc.subjectnonhuman
dc.subjectpolymerase chain reaction
dc.subjectpriority journal
dc.subjectquantitative analysis
dc.subjectsignal transduction
dc.subjectupregulation
dc.subjectWestern blotting
dc.subjectWnt signaling
dc.subjectanimal
dc.subjectcardiac muscle
dc.subjectcardiac muscle cell
dc.subjectcell differentiation
dc.subjectcell line
dc.subjectcell nucleus
dc.subjectcell proliferation
dc.subjectcytology
dc.subjectdeficiency
dc.subjectdisease model
dc.subjectgenetics
dc.subjecthuman embryonic stem cell
dc.subjectmetabolism
dc.subjectpathology
dc.subjectphenotype
dc.subjectprotein transport
dc.subjectWnt signaling
dc.subjectAdult
dc.subjectAnimals
dc.subjectbeta Catenin
dc.subjectCadherins
dc.subjectCell Differentiation
dc.subjectCell Line
dc.subjectCell Nucleus
dc.subjectCell Proliferation
dc.subjectDisease Models, Animal
dc.subjectHuman Embryonic Stem Cells
dc.subjectHumans
dc.subjectMice
dc.subjectMyocardium
dc.subjectMyocytes, Cardiac
dc.subjectPhenotype
dc.subjectProtein Transport
dc.subjectPyridines
dc.subjectPyrimidines
dc.subjectRNA, Messenger
dc.subjectUp-Regulation
dc.subjectWnt Signaling Pathway
dc.typeArticle
dc.contributor.departmentDEPT OF BIOLOGICAL SCIENCES
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.1186/s13287-018-1086-8
dc.description.sourcetitleStem Cell Research and Therapy
dc.description.volume9
dc.description.issue1
dc.description.page338
dc.published.statePublished
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