title: The RNA-binding protein PCBP2 inhibits Ang II-induced hypertrophy of cardiomyocytes though promoting GPR56 mRNA degeneration.
abstract: Poly(C)-binding proteins (PCBPs) are known as RNA-binding proteins that interact in a sequence-specific fashion with single-stranded poly(C). This family can be divided into two groups: hnRNP K and PCBP1-4. PCBPs are expressed broadly in human and mouse tissues and all members of the PCBP family are related evolutionarily. However, their physiological or pathological functions in the hearts remain unknown. Here we reported that PCBP2 is an anti-hypertrophic factor by inhibiting GPR56 mRNA stability. We found the downregulation of PCBP2 in human failing hearts and mouse hypertrophic hearts. PCBP2 knockdown promoted angiotensin II (Ang II)-induced hypertrophy (increase in cell size, protein synthesis and activation of fetal genes) of neonatal cardiomyocytes and H9C2 cells, while PCBP2 overexpression obtained oppose effects. Furthermore, PCBP2 was shown to inhibit GPR56 expression by promoting its mRNA degeneration in cardiomyocytes. Finally, we knocked down GPR56 in cardiomyocytes and found that GPR56 promoted Ang II-induced cardiomyocyte hypertrophy and it contributed to PCBP2 effects on cardiomyocyte hypertrophy.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Si
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: jumei1960@163.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049108:Cell Enlargement; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000804:Angiotensin II; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D043562:Receptors, G-Protein-Coupled; C118925:ADGRG1 protein, human; C527491:Adgrg1 protein, rat; C524781:Adgrg1 protein, mouse; C501903:PCBP2 protein, human; C501904:Pcbp2 protein, mouse; C571107:poly(rC) binding protein 2, rat
keywords: Angiotensin II; Cardiomyocyte hypertrophy; GRP56; PCBP2