fig5

The WNT/β-catenin pathway regulates expression of the genes involved in cell cycle progression and mitochondrial oxidative phosphorylation in the postmitotic cardiac myocytes

Figure 5. cWNT/β-catenin activation induces cell cycle reentry in postmitotic cardiac myocytes. (A) GSEA map depicting enrichment of the E2F targets in the DEGs in the β-catenin activated cardiac myocytes compared to the wild-type myocytes. (B) RT-PCR validation of the E2F target genes showing significant upregulation of cell proliferation markers in the β-catenin activated cardiac myocytes (n = 5). (C) Myocardial sections stained for phospho-histone 3 (pH3), a marker of proliferation, and PCM1, which tags cardiac myocytes in the heart in the experimental groups. (D) Representative immunofluorescence panels of thin myocardial sections stained for Ki-67, a marker of proliferation, and co-stained with PCM1, a marker for cardiac myocytes. (E) Enlarged images of Myh6-Mcm:Ctnnb1GoF myocardial sections showing co-staining of Ki-67 (MKI67) and PCM1. (F-H) Quantitative data showing the comparison of the PH3 positive nuclei, Ki-67-stained nuclei, Ki-67, and PCM1 co-stained nuclei, as well as PCM1 positive nuclei between the wild type, Myh6-Mcm, Myh6-Mcm:Ctnnb1LoF, and Myh6-Mcm:Ctnnb1GoF hearts (n = 5). (I) Representative immunofluorescence panels showing cardiac myocytes stained for PCM1 in the myocardial sections of WT, Myh6-Mcm, Myh6-Mcm:Ctnnb1LoF, and Myh6-Mcm:Ctnnb1GoF mice. (J) Quantitative data showing the number of nuclei expressing PCM1 in the experimental groups, which was unchanged. RT-PCR: Reverse transcription-polymerase chain reaction; GSEA: Gene Set Enrichment Analysis; DEGs: differentially expressed genes; PCM1: pericentriolar material protein 1; WT: wild type; Myh6-Mcm: myosin heavy chain 6-MerCreMer.

The Journal of Cardiovascular Aging

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