RACK1 contributes to the upregulation of embryonic genes in a model of cardiac hypertrophy

• Published in: Scientific reports 2024-10, Vol.14 (1), p.25698-17, Article 25698
• Main Authors: Ceci, Marcello, Bonvissuto, Davide, Papetti, Flavia, Silvestri, Federica, Sette, Claudio, Catalani, Elisabetta, Cervia, Davide, Gornati, Rosalba, Romano, Nicla
• Format: Article
• Language: English
• Subjects: 631/136; 631/45; 631/80; Animals; Cardiac hypertrophy; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cell culture; Disease Models, Animal; Down-regulation; GATA4; Gene expression; Gene Expression Regulation, Developmental - drug effects; Growth factors; Heart; Humanities and Social Sciences; Hypertrophy; Kinases; multidisciplinary; NF-AT protein; NFAT2; Phenylephrine; Phenylephrine - pharmacology; Protein kinase C; RACK1; Receptors for Activated C Kinase - genetics; Receptors for Activated C Kinase - metabolism; Science; Science (multidisciplinary); Signal Transduction; Transfection; Up-Regulation; WT1; Zebrafish; Zebrafish - embryology; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-76138-x

Receptors for activated C kinases (RACKs) have been shown to coordinate PKC-mediated hypertrophic signalling in mice. However, little information is available on its participation in embryonic gene expression. This study investigated the involvement of RACK1 in the expression of embryonic genes in a zebrafish (ZF) ex vivo heart culture model by using phenylephrine (PE) or a growth factors cocktail (GFs) as a prohypertrophic/regeneration stimulus. Blebbistatin (BL) inhibition has also been studied for its ability to block the signal transduction actions of some PEs. qRT‒PCR and immunoblot analyses confirmed the upregulation of RACK1 in the PE- and GFs-treated groups. BL administration counteracted PE-induced hypertrophy and downregulated RACK1 expression. Immunohistochemical analyses of the heart revealed the colocalization of RACK1 and embryonic genes, namely, Gata4, Wt1, and Nfat2, under stimulation, whereas these genes were expressed at lower levels in the BL treatment group. Culturing ZF heart cells activated via GFs treatment increased the expression of RACK1. The overexpression of RACK1 induced by the transfection of recombinant RACK1 cDNA in ZF heart cells increased the expression of embryonic genes, especially after one week of GFs treatment. In summary, these results support the involvement of RACK1 in the induction of embryonic genes during cardiac hypertrophy/GFs stimulation in a fish heart model, which can be used as an alternative study model for mammals.