P2Y 2 Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling

• DOI: 10.1161/circresaha.117.310812
• Publication Date: 2017-09-19T00:30:35Z
• Authors: Farid G. Khalafalla; Steven Greene; Hashim Khan; Kelli Ilves; Megan M. Monsanto; Roberto Alvarez; Monica Chavarria; Jonathan Nguyen; Benjamin Norman; Walter P. Dembitsky; Mark A. Sussman
• Keywords: P2Y receptor; Purinergic Signalling; Hippo signaling pathway

Autologous stem cell therapy using human c-Kit+ cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged patients with HF genetic predispositions and comorbidities chronic diseases exhibit poor proliferative migratory capabilities, which impair overall reparative potential injured myocardium. Therefore, empowering functionally compromised proregenerative molecules ex vivo crucial improving the outcome in HF.To improve hCPC proliferation migration responses that are critical regeneration by targeting P2Y2 nucleotide receptor (P2Y2R) activated extracellular ATP UTP released following injury/stress.c-Kit+ were isolated tissue undergoing left ventricular assist device implantation surgery. Correlations between P2 expression growth kinetics revealed downregulation select receptors, including P2Y2R, slow-growing compared fast growers. significantly improved overexpressing or stimulating P2Y2R. Mechanistically, P2Y2R-induced dependent on activation YAP (yes-associated protein)-the downstream effector Hippo signaling pathway.Proliferation impaired enhanced P2Y2R-mediated activation, revealing novel link nucleotides during injury/stress signaling-a central regulator regeneration. Functional correlations exist phenotypic properties purinergic expression. Lack P2Y2R other stress detectors could compromise responsiveness to presence signals. These findings set stage subsequent studies assess modulation as strategy use HF.