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.

The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the “Ominous Octet” theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting β cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.

Objectives. This study was designed to explore the intellectual landscape of research into the application of sphingosine 1 phosphate (S1P) in age-related diseases and to identify thematic development trends and research frontiers in this area. Methods. Scientometric research was conducted by analyzing bibliographic records retrieved from the Web of Science (WOS) Sci-Expanded Database dated between 1900 and 2020. Countries, institutions, authors, keyword occurrence analysis, and cooperation network analysis were performed using the CiteSpace and VOSviewer software. Results. A total of 348 valid records were included in the final dataset, and the number of publications and the frequency of citations have grown rapidly over the last ten years. The USA ( n = 175 ), China ( n = 42 ), and Germany ( n = 37 ) were the three largest contributors to the global publications on S1P and aging, while the Medical University of South Carolina ( n = 15 ), University of California, San Francisco ( n = 13 ), and University of Toronto ( n = 13 ) were the leading institutions in this field. Analysis showed that early studies primarily focused on the mechanism of S1P intervention in AD. While S1P and its relevant metabolites have remained a long-term active area of research, recent studies have focused more on interventions aimed at improving retinal degeneration, cardiomyopathy, multiple sclerosis, and diabetes, among others. Conclusions. It is worth mentioning that this manuscript is the first to describe any bibliometric analysis of S1P and its application in age-related interventions. This study includes a discussion of the (1) historical overview of the topic; (2) main contributors: journals, countries, institutes, funding agencies, and authors; (3) collaboration between institutes and authors; (4) research hot spots and zones; and 5) research trends and frontiers. This will enable scholars to understand the current status of S1P research in age-related diseases.

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