Wnt2bb Induces Cardiomyocyte Proliferation in Zebrafish Hearts via the jnk1/c-jun/creb1 Pathway

Copyright © 2020 Peng, Fan, Tan, Zeng, Su, Zhang, Yang, Xia, Fan, Cai and Tang..

Previous studies have demonstrated that inhibition of canonical Wnt signaling promotes zebrafish heart regeneration and that treatment of injured heart tissue with the Wnt activator 6-bromo-indirubin-3-oxime (BIO) can impede cardiomyocyte proliferation. However, the mechanism by which Wnt signaling regulates downstream gene expression following heart injury remains unknown. In this study, we have demonstrated that inhibition of injury-induced myocardial wnt2bb and jnk1/creb1/c-jun signaling impedes heart repair following apex resection. The expression of jnk1, creb1, and c-jun were inhibited in wnt2bb dominant negative (dn) mutant hearts and elevated in wnt2bb-overexpresssing hearts following ventricular amputation. The overexpression of creb1 sufficiently rescued the dn-wnt2bb-induced phenotype of reduced nkx2.5 expression and attenuated heart regeneration. In addition, wnt2bb/jnk1/c-jun/creb1 signaling was increased in Tg(hsp70l:dkk1) transgenic fish, whereas it was inhibited in Tg(hsp70l:wnt8) transgenic fish, indicating that canonical Wnt and non-canonical Wnt antagonize each other to regulate heart regeneration. Overall, the results of our study demonstrate that the wnt2bb-mediated jnk1/c-jun/creb1 non-canonical Wnt pathway regulates cardiomyocyte proliferation.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:8

Enthalten in:

Frontiers in cell and developmental biology - 8(2020) vom: 05., Seite 323

Sprache:

Englisch

Beteiligte Personen:

Peng, Xiangwen [VerfasserIn]
Fan, Shunyang [VerfasserIn]
Tan, Jing [VerfasserIn]
Zeng, Zhi [VerfasserIn]
Su, Meiling [VerfasserIn]
Zhang, Yuan [VerfasserIn]
Yang, Ming [VerfasserIn]
Xia, Luoxing [VerfasserIn]
Fan, Xuejiao [VerfasserIn]
Cai, Weibin [VerfasserIn]
Tang, Wai Ho [VerfasserIn]

Links:

Volltext

Themen:

C-jun
C-jun/jnk1/creb1
Creb1
Journal Article
Nkx2.5
Nkx25
Wnt2bb
Zebrafish heart regeneration

Anmerkungen:

Date Revised 28.09.2020

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.3389/fcell.2020.00323

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM311032192