scholarly journals The role of wnt signalling pathway in cardiomyocytes

2016 ◽  
Author(s):  
Κωνσταντίνος Ψαρρός

Το Wnt σηματοδοτικό μονοπάτι αποτελεί τον κύριο ρυθμιστή για μια πληθώρα κυτταρικών διεργασιών. Πρόσφατα δύο «μη κανονικά» Wnt σηματοδοτικά μονοπάτια. Αυτά είναι γνωστά ως το Planar Cell Polarity pathway (PCP) και το Calcium dependant pathway (CDP). Το Wnt5a είναι μια πρωτεΐνη που ενεργοποιεί εκλεκτικά τα μη κανονικά Wnt σηματοδοτικά μονοπάτια, ενώ ρυθμιστής της αποτελεί το Sfrp5. Ο ρόλος τους στο καρδιαγγειακό σύστημα και πιο συγκεκριμένα στην οξειδοαναγωγική κατάσταση του μυοκαρδίου δεν έχει ακόμα εξερευνηθεί.Η εξωγενής χορήγηση Wnt5a αλλά και η ενδογενής υπερέκφραση του σε κύτταρα H9C2 οδήγησαν σε αυξημένη παραγωγή υπεροξειδικών ριζών προερχόμενων από το ένζυμο NADPH οξειδάση. Επιπλέον η εξωγενής χορήγηση wnt5a ενεργοποιεί το CDP μέσω της CamKII αλλά και του PCP μέσω του Rac1. Επιπλέον, στο κυτταρικό μοντέλο υπερέκφρασης του Wnt5a παρατηρήθηκε και φωσφωρυλίωση της JNK αλλά και υπερτροφικός φαινότυπος κατά την διαφοροποίησή τους λόγω αυξημένης συγκέντρωσης ενδοκυτταρικού ασβεστίου. Τα αποτελέσματα επιβεβαιώθηκαν περεταίρω και με την χρήση αναστολέων για το μονοπάτι CDP και του PCP. Τα αποτελέσματα της έρευνας αυτής υποδεικνύουν τον ρόλο του Wnt5a ως ρυθμιστή της οξειδοαναγωγικής κατάστασης στην καρδιά, καθιστώντας τo Wnt5a και τα μη κανονικά Wnt σηματοδοτικά μονοπάτια πιθανούς θεραπευτικούς στόχους για το οξειδωτικό στρες και την καρδιακή υπερτροφία.

2015 ◽  
Vol 1615 ◽  
pp. 22-30 ◽  
Author(s):  
Xiao-yu Yang ◽  
Kai Jin ◽  
Rui Ma ◽  
Juan-mei Yang ◽  
Wen-wei Luo ◽  
...  

Author(s):  
Rubin S Baskir ◽  
Amanda G Hansen ◽  
Ethan Lee

2009 ◽  
Vol 126 ◽  
pp. S156
Author(s):  
Laura L. Yates ◽  
Carsten Schnatwinkel ◽  
Jennifer N. Murdoch ◽  
Debora Bogani ◽  
Caroline J. Formstone ◽  
...  

2013 ◽  
Vol 457 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Roberto Mayor ◽  
Eric Theveneau

The neural crest is an embryonic stem cell population whose migratory behaviour has been likened to malignant invasion. The neural crest, as does cancer, undergoes an epithelial-to-mesenchymal transition and migrates to colonize almost all the tissues of the embryo. Neural crest cells exhibit collective cell migration, moving in streams of high directionality. The migratory neural crest streams are kept in shape by the presence of negative signals in their vicinity. The directionality of the migrating neural crest is achieved by contact-dependent cell polarization, in a phenomenon called contact inhibition of locomotion. Two cells experiencing contact inhibition of locomotion move away from each other after collision. However, if the cell density is high only cells exposed to a free edge can migrate away from the cluster leading to the directional migration of the whole group. Recent work performed in chicks, zebrafish and frogs has shown that the non-canonical Wnt–PCP (planar cell polarity) pathway plays a major role in neural crest migration. PCP signalling controls contact inhibition of locomotion between neural crest cells by localizing different PCP proteins at the site of cell contact during collision and locally regulating the activity of Rho GTPases. Upon collision RhoA (ras homologue family member A) is activated, whereas Rac1 is inhibited at the contact between two migrating neural crest cells, leading to the collapse of protrusions and the migration of cells away from one another. The present review summarizes the mechanisms that control neural crest migration and focuses on the role of non-canonical Wnt or PCP signalling in this process.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Meng Li ◽  
Weiman Gao ◽  
Le Ji ◽  
Jia Li ◽  
Wanting Jiang ◽  
...  

Objective. Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. Methods. Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. Results. Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. Conclusion. Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.


2021 ◽  
Vol 22 (19) ◽  
pp. 10840
Author(s):  
Jasna Lojk ◽  
Janja Marc

The Wnt signalling pathway is one of the central signalling pathways in bone development, homeostasis and regulation of bone mineral density. It consists of numerous Wnt ligands, receptors and co-receptors, which ensure tight spatiotemporal regulation of Wnt signalling pathway activity and thus tight regulation of bone tissue homeostasis. This enables maintenance of optimal mineral density, tissue healing and adaptation to changes in bone loading. While the role of the canonical/β-catenin Wnt signalling pathway in bone homeostasis is relatively well researched, Wnt ligands can also activate several non-canonical, β-catenin independent signalling pathways with important effects on bone tissue. In this review, we will provide a thorough overview of the current knowledge on different non-canonical Wnt signalling pathways involved in bone biology, focusing especially on the pathways that affect bone cell differentiation, maturation and function, processes involved in bone tissue structure regulation. We will describe the role of the two most known non-canonical pathways (Wnt/planar cell polarity pathways and Wnt/Ca2+ pathway), as well as other signalling pathways with a strong role in bone biology that communicate with the Wnt signalling pathway through non-canonical Wnt signalling. Our goal is to bring additional attention to these still not well researched but important pathways in the regulation of bone biology in the hope of prompting additional research in the area of non-canonical Wnt signalling pathways.


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