Agrin-Mediated Cardiac Regeneration: Some Open Questions
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 i...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-06-01
|
Series: | Frontiers in Bioengineering and Biotechnology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.00594/full |
id |
doaj-b5238186e416403fa9e14a7f31973832 |
---|---|
record_format |
Article |
spelling |
doaj-b5238186e416403fa9e14a7f319738322020-11-25T03:18:46ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-06-01810.3389/fbioe.2020.00594539814Agrin-Mediated Cardiac Regeneration: Some Open QuestionsMaria Giulia Bigotti0Maria Giulia Bigotti1Katie L. Skeffington2Ffion P. Jones3Massimo Caputo4Andrea Brancaccio5Andrea Brancaccio6Bristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Bristol, United KingdomSchool of Biochemistry, University of Bristol, Bristol, United KingdomBristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Bristol, United KingdomBristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Bristol, United KingdomBristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Bristol, United KingdomSchool of Biochemistry, University of Bristol, Bristol, United KingdomInstitute of Chemical Sciences and Technologies “Giulio Natta” (SCITEC)—CNR, Rome, ItalyAfter 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.https://www.frontiersin.org/article/10.3389/fbioe.2020.00594/fullheart regenerationagrindystrophin-glycoprotein complexdystroglycanlamininYAP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Giulia Bigotti Maria Giulia Bigotti Katie L. Skeffington Ffion P. Jones Massimo Caputo Andrea Brancaccio Andrea Brancaccio |
spellingShingle |
Maria Giulia Bigotti Maria Giulia Bigotti Katie L. Skeffington Ffion P. Jones Massimo Caputo Andrea Brancaccio Andrea Brancaccio Agrin-Mediated Cardiac Regeneration: Some Open Questions Frontiers in Bioengineering and Biotechnology heart regeneration agrin dystrophin-glycoprotein complex dystroglycan laminin YAP |
author_facet |
Maria Giulia Bigotti Maria Giulia Bigotti Katie L. Skeffington Ffion P. Jones Massimo Caputo Andrea Brancaccio Andrea Brancaccio |
author_sort |
Maria Giulia Bigotti |
title |
Agrin-Mediated Cardiac Regeneration: Some Open Questions |
title_short |
Agrin-Mediated Cardiac Regeneration: Some Open Questions |
title_full |
Agrin-Mediated Cardiac Regeneration: Some Open Questions |
title_fullStr |
Agrin-Mediated Cardiac Regeneration: Some Open Questions |
title_full_unstemmed |
Agrin-Mediated Cardiac Regeneration: Some Open Questions |
title_sort |
agrin-mediated cardiac regeneration: some open questions |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Bioengineering and Biotechnology |
issn |
2296-4185 |
publishDate |
2020-06-01 |
description |
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. |
topic |
heart regeneration agrin dystrophin-glycoprotein complex dystroglycan laminin YAP |
url |
https://www.frontiersin.org/article/10.3389/fbioe.2020.00594/full |
work_keys_str_mv |
AT mariagiuliabigotti agrinmediatedcardiacregenerationsomeopenquestions AT mariagiuliabigotti agrinmediatedcardiacregenerationsomeopenquestions AT katielskeffington agrinmediatedcardiacregenerationsomeopenquestions AT ffionpjones agrinmediatedcardiacregenerationsomeopenquestions AT massimocaputo agrinmediatedcardiacregenerationsomeopenquestions AT andreabrancaccio agrinmediatedcardiacregenerationsomeopenquestions AT andreabrancaccio agrinmediatedcardiacregenerationsomeopenquestions |
_version_ |
1724625945898254336 |