The WNT/β-Catenin Pathway Regulates Expression of the Genes Involved in Cell Cycle Progression and Mitochondrial Oxidative Phosphorylation in the Postmitotic Cardiac Myocytes

Authors

Melis Olcum
Sirisha M Cheedipudi
Leila Rouhi
Siyang Fan
Hyun-Hwan Jeong
Zhongming Zhao
Priyatansh Gurha
Ali J Marian

Publication Date

1-1-2022

Journal

The Journal of Cardiovascular Aging

Abstract

INTRODUCTION: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown.

AIM: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes.

METHODS AND RESULTS: Cardiac myocyte-specific tamoxifen-inducible MerCreMer (

CONCLUSION: Activation of the β-catenin of the cWNT pathway in postmitotic myocytes leads to cell cycle reentry and expression of genes involved in cytokinesis without leading to an increase in the number of myocytes. In contrast, suppression of the β-catenin modestly increases the expression of genes involved in oxidative phosphorylation. The findings provide insights into the role of β-catenin of the cWNT pathway in the regulation of cell cycle reentry and oxidative phosphorylation in the postmitotic cardiac myocytes.

Keywords

Myocyte proliferation, WNT signaling, beta-catenin, cytokinesis, cell cycle, oxidative phosphorylation, mitochondria

DOI

10.20517/jca.2021.35

PMID

35224561

PMCID

PMC8874274

PubMedCentral® Posted Date

2-25-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes