Progesterone and AdipoQ Receptor 11 Links Ras Signaling to Cardiac Development in Zebrafish

Abstract

Objective-Progesterone and adipoQ receptor (PAQR) 10 and PAQR11 are 2 highly homologous genes involved in compartmentalized Ras signaling in the Golgi apparatus. The aim of this study was to investigate the physiological functions of PAQR10 and PAQR11. Methods and Results-We used zebrafish as a model system to analyze the potential function of PAQR10/PAQR11. The expression profiles of PAQR10 and PAQR11 in zebrafish embryos are overlapping in many areas, but only PAQR11 is expressed in the developing heart. Knockdown of PAQR11 but not PAQR10 in zebrafish embryos causes cardiac developmental defects, including dilation of cardiac chambers, abnormal heart looping, disruption of atrioventricular cushion formation, heart edema, and blood regurgitation. PAQR11 knockdown markedly reduces the number and proliferation rate of cardiomyocytes and alters the morphology of myocardial cells during early heart development. The cardiac defects caused by PAQR11 knockdown can be phenocopied by MEK inhibitors and a dominant negative Ras. Furthermore, constitutively active Ras and especially a Golgi-localized but not a plasma membrane-localized Ras are able to rescue the cardiac defects caused by PAQR11 knockdown. Conclusion-This study not only provides in vivo evidence that PAQR11 plays a critical role in heart morphogenesis but also pinpoints the importance of compartmentalized Ras signaling during development. (Arterioscler Thromb Vasc Biol. 2012;32:2158-2170.)

Expression of SPARC and the osteopontin‐like protein during skeletal development in the cichlid fish Oreochromis mossambicus

“…Bobes and Goetz's findings in the ovary and testis of adult trout may indicate that OP-L is only expressed in functional organs and not during developmental stages. Moreover, we also could not confirm the occurrence of OP-L during cardiac development for O. mossambicus in contrast to zebrafish, where it regulates cell migration during atrioventricular canal formation (Just et al, 2011;Huang et al, 2012;Banjo et al, 2013). However, we confirmed the reports of Fonseca et al (2007), that OP-L is not expressed in the intestine, stomach, spleen, and brain of teleost fishes.…”

“…Some researchers describe its expression restricted to only a few soft tissues (Fonseca et al, 2007), whereas others report it present in several soft tissues: e.g., ovary (during ovulation), testis, and in small amounts in the kidney, gills, brain, and skin of trout (Bobe and Goetz, 2001). Moreover, OP-L seems to function specifically in cardiac tissue during zebrafish development (Just et al, 2011;Huang et al, 2012;Banjo et al, 2013). The inconsistency among these studies might be due to the focus on selected developmental stages along with the focus on specific tissues and the analysis methods used for adult tissues.…”

Progesterone Receptor Signaling Selectively Modulates Cytokine-Induced Global Gene Expression in Human Cervical Stromal Cells

“…interleukin-1 receptor-associated kinase 3 6.77 2.5 19.75 Negative regulator of Toll/interleukin receptor signal transduction (Kobayashi et al, 2002); prevents neutrophil-dependent lung injury during influenza infection of the respiratory tract (Seki et al, 2010) MMD monocyte to macrophage differentiationassociated 5.42 2.48 9.64 Up-regulated during monocyte differentiation (Rehli et al, 1995); induced by lipopolysaccharide in macrophages (Liu et al, 2012); enhances cytokine and nitric oxide production in macrophages (Liu et al, 2012); plays a critical role in heart morphogenesis (Huang et al, 2012); inhibits growth of lung cancer cells (Li and He, 2014 (Chen et al, 2008); induced by preovulatory LH surge in ovarian steroidogenic cells (Christenson et al, 2013 Functions in the cellular import of zinc at the onset of inflammation (Begum et al, 2002); NF-κB target gene that suppresses inflammatory signaling in zinc-dependent fashion (Liu et al, 2013).…”

The significant role of the Golgi apparatus in cardiovascular diseases

“…Therefore, decreased activity of GlcAT‐I impaired heart development and resulted in congenital heart defects through suppressing proteoglycan synthesis. Huang et al () emphasized that Golgi‐localized but not plasma membrane‐localized Ras was crucial for cardiac development in zebrafish. Moreover, the Fukutin‐related protein (FKRP) was also localized in the GA in myofibers.…”