Apelin is an endogenous peptide that is a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1). The apelin/APJ system is distributed in diverse periphery organ tissues. It has been shown that the apelin/APJ system plays various roles in physiology and pathophysiology of many organs. It regulates cardiovascular development or cardiac disease, glycometabolism and fat metabolism as well as metabolic disease. The apelin/APJ system participates in various cell activities such as proliferation, migration, apoptosis or inflammation. However, apelin/APJ function in the liver is still under investigation. In the liver, the apelin-APJ system could play an inhibitory role in liver regeneration and promote Fas-induced apoptosis. It may participate in the formation of hepatic fibrosis or cirrhosis, and even cancer. In this review, we summarize the role of the apelin/APJ system in liver disease.
Edited by Ned ManteiKeywords: GC box Proliferation Vascular smooth muscle cell Y-box binding protein 1 a b s t r a c t Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in atherosclerosis and restenosis. In this paper, we report that Y-box binding protein 1 (YB1) functions as a phenotypic regulator in VSMC proliferation-differentiation switching through targeting GC box-dependent genes. Oligo pull-down assays demonstrated that YB1 binds directly to GC boxes via amino acids 125-220. YB1 C-terminal tail domain (CTD, amino acids 125-324) regulates GC box-dependent target gene transcription and suppresses VSMC proliferation. These findings provide a novel insight into the regulation of GC box-related genes by YB1, and provide a new understanding of VSMC proliferation regulation.
Apelin participates in cardiovascular functions, metabolic disease, and homeostasis disorder. However, the biological function of apelin in liver diseases, especially liver fibrosis is still under investigation. The present study aimed to investigate the expression of apelin in nonalcoholic fatty liver disease (NAFLD) and the mechanism of apelin promoting hepatic fibrosis through ERK signaling in hepatic stellate LX-2 cells. The results showed that the ALT and AST levels in serum were increased in the mice fed HFC. The histological staining revealed that hepatocellular steatosis and ballooning degeneration was severe, and fibrogenesis appeared as increased pericellular collagen deposition along with pericentral (lobular) collagen deposition in the mice fed HFC. Immunochemistry and qRT-PCR results showed that the expression of apelin and profibrotic genes was higher as compared to the control group. The in vitro experiments demonstrated that apelin-13 upregulated the transcription and translation levels of collagen type I (collagen-I) and α-smooth muscle actin (α-SMA) in LX-2 cells. The immunofluorescent staining, qRT-PCR, and Western blot results showed that the overexpression of apelin markedly increased the expression of α-SMA and cyclinD1. The LX-2 cells treated with apelin-13 displayed an increased expression of pERK1/2 in a time-dependent manner, while the pretreatment with PD98059 abolished the apelin-induced expression of α-SMA and cyclinD1. Furthermore, the in vivo and in vitro assays suggested a key role of apelin in promoting liver fibrosis, and the underlying mechanism might be ascribed to the apelin expression of profibrotic genes via ERK signaling pathway.Electronic supplementary materialThe online version of this article (10.1007/s11010-019-03581-0) contains supplementary material, which is available to authorized users.
Previous studies have demonstrated that both retinoids and apelin possess potent cardiovascular properties and that retinoids can mediate the expression of many genes in the cardiovascular system. However, it is not clear whether and how retinoids regulate apelin expression in rat VSMCs (vascular smooth muscle cells). In the present study, we investigated the molecular mechanism of apelin expression regulation by the synthetic retinoid Am80 in VSMCs. The results showed that Am80 markedly up-regulated apelin mRNA and protein levels in VSMCs. Furthermore, KLF5 (Krüppel-like factor 5) and Sp1 (stimulating protein-1) co-operatively mediated Am80-induced apelin expression through their direct binding to the TCE (transforming growth factor-β control element) on the apelin promoter. Interestingly, upon Am80 stimulation, the RARα (retinoic acid receptor α) was recruited to the apelin promoter by interacting with KLF5 and Sp1 prebound to the TCE site of the apelin promoter to form a transcriptional activation complex, subsequently leading to the up-regulation of apelin expression in VSMCs. An in vivo study indicated that Am80 increased apelin expression in balloon-injured arteries of rats, consistent with the results from the cultured VSMCs. Thus the results of the present study describe a novel mechanism of apelin regulation by Am80 and further expand the network of RARα in the retinoid pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.