Agrin-Mediated Cardiac Regeneration: Some Open Questions.
Hippo pathway
YAP
agrin
cardiomyocyte proliferation
dystroglycan
dystrophin-glycoprotein complex
heart regeneration
laminin
Journal
Frontiers in bioengineering and biotechnology
ISSN: 2296-4185
Titre abrégé: Front Bioeng Biotechnol
Pays: Switzerland
ID NLM: 101632513
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
03
2020
accepted:
15
05
2020
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
3
7
2020
Statut:
epublish
Résumé
After cardiac injury, the mammalian adult heart has a very limited capacity to regenerate, due to the inability of fully differentiated cardiomyocytes (CMs) to efficiently proliferate. This has been directly linked to the extracellular matrix (ECM) surrounding and connecting cardiomyocytes, as its increasing rigidity during heart maturation has a crucial impact over the proliferative capacity of CMs. Very recent studies using mouse models have demonstrated how the ECM protein agrin might promote heart regeneration through CMs de-differentiation and proliferation. In maturing CMs, this proteoglycan would act as an inducer of a specific molecular pathway involving ECM receptor(s) within the transmembrane dystrophin-glycoprotein complex (DGC) as well as intracellular Yap, an effector of the Hippo pathway involved in the replication/regeneration program of CMs. According to the mechanism proposed, during mice heart development agrin gets progressively downregulated and ultimately replaced by other ECM proteins eventually leading to loss of proliferation/ regenerative capacity in mature CMs. Although the role played by the agrin-DGC-YAP axis during human heart development remains still largely to be defined, this scenario opens up fascinating and promising therapeutic avenues. Herein, we discuss the currently available relevant information on this system, with a view to explore how the fundamental understanding of the regenerative potential of this cellular program can be translated into therapeutic treatment of injured human hearts.
Identifiants
pubmed: 32612983
doi: 10.3389/fbioe.2020.00594
pmc: PMC7308530
doi:
Types de publication
Journal Article
Langues
eng
Pagination
594Subventions
Organisme : British Heart Foundation
ID : CH/17/1/32804
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/15/33/31394
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 Bigotti, Skeffington, Jones, Caputo and Brancaccio.
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