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Turkish Journal of Biology

Abstract

MEIS1, a member of the TALE-type homeobox gene family, has emerged as a pivotal regulator of cardiomyocyte cell cycle arrest and represents a promising therapeutic target. Our study reveals that inhibition of MEIS1 using two novel small molecules, MEISi-1 and MEISi-2, significantly enhances neonatal cardiomyocyte proliferation and cytokinesis. Specifically, MEISi-1 and MEISi-2 increased the proportion of proliferating cardiomyocytes (Ph3+TnnT cells) upto 4.5 fold and the percentage of cytokinetic cardiomyocytes (AuroraB+TnnT cells) by 2 fold, compared to untreated controls. MEIS1 inhibition resulted in a notable downregulation of MEIS1 target genes and cyclin-dependent kinase inhibitors, demonstrating its effect on key regulatory pathways. Additionally, the culture and differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes were studied, with MEIS1 inhibition showing no adverse effects on cell viability. Extended treatment with MEIS inhibitors led to a substantial upregulation of critical cardiac-specific genes, including a 15-fold increase in the expression of Nkx2.5. This upregulation significantly impacted both cardiac mesoderm and cardiac progenitor cells. These findings underscore the potential of MEIS1 inhibitors as effective agents in enhancing cardiac regeneration and highlight their therapeutic promise in regenerative cardiology.

Author ORCID Identifier

AYNURA MAMMADOVA: 0000-0003-0569-9482

GALİP ASLAN: 0000-0002-5084-1241

LI MO: 0000-0003-4449-3583

QIFANG WU: 0000-0003-4244-9466

SEBASTIAN CLAUSS: 0000-0002-5675-6128

FATİH KOCABAŞ: 0000-0001-8096-6056

DOI

10.55730/1300-0152.2716

Keywords

MEIS1, cardiac regeneration, cardiac protection, cardiomyocyte proliferation

First Page

414

Last Page

431

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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