Unit:
Τομέας Βασικών ΕπιστημώνLibrary of the School of Health Sciences
Author:
Ψαρρός Κωνσταντίνος
Dissertation committee:
Επίκουρη Καθηγήτρια Μ. Σιμοπούλου, Μ Κουτσιλιέρης, Α Φιλίππου
Original Title:
The role of wnt signalling pathway in cardiomyocytes
Translated title:
Ο ρόλος του μη κανονικού Wnt σηματοδοτικού μονοπατιού στα μυοκαρδιακά κύτταρα
Summary:
The Wnt signalling pathway is a major regulator of many cell functions
including proliferation, differentiation and migration. Recently, apart from
the canonical pathway which utilizes β-catenin, two β-catenin independent
pathways have been reported. These are termed as Wnt non canonical signaling
pathways. They further branch to into the a) planar cell polarity pathway
(PCP), where Rac1 and JNK are the main signalling molecules and to b) the
calcium dependant pathway (CDP) that is mediated through intracellular calcium
concertation and CamKII. Wnt5a is part of the Wnt proteins that can selectively
activate Wnt non-canonical signalling and it is extracellularly regulated by
Sfrp5. Although these pathways are mostly associated with embryonic development
and cancer, little information is known about their role in the adult heart. In
this study we investigated whether Wnt5a activation of the Wnt non-canonical
pathways can regulate myocardial redox state.
To this purpose we used the H9C2 rat cardiomyoblast cell line. Interestingly
Wnt5a treatments did increase superoxide in both exogenous treatments and from
endogenous overexpression in a Wnt5a overexpressing differentiated H9C2 cells.
Activation of both PCP and CDP pathways occurred but JNK phosphorylation was
observed only in the transfected cells. These effects were reversed by use of a
Rac1 and PLC inhibitor. Furthermore in the Wnt5a transfected cells we observed
a hypertrophic phenotype and increase intracellular Ca2+ concentration. Finally
we were able to further validate our findings using myocardial samples from
transgenic mice overexpressing Wnt5a.
Our findings suggest that Wnt5a through activation of the non-canonical
pathways can be a major regulator of myocardial redox state, thus proving a
potential therapeutic target for both redox and hypertrophy related diseases.
Keywords:
Cardiomyocytes, Oxidative stress, Wnt signalling, Cardiovascular Disease, Hypertrophy
Number of references:
156
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