RESUMEN
Placentation requires the production of numerous growth factors, hormones and transcription factors. Many of them, like the adipose tissuederived leptin or adiponectin, have been identified in the placenta and their role has been established in the proliferation and subsequent development of the placenta. Apelin is another adipokine known for proliferative effects in different cell types. PCR, immunoblotting and immunocytochemistry were used to study mRNA and protein expression of apelin and its receptor (APJ) in syncytiotrophoblast (BeWo) and cytotrophoblast (JEG3) cells as well in immunohistochemistry in human normal placenta slides. The effect of apelin on cell proliferation study was investigated by alamarBlue® and Cell Counting Kit8 assays, the cell cycle by the flow cytometry method and the protein expression of cyclins and phosphorylation level of extracellular signalregulated kinases (ERK)1/2, phosphatidylinositol 3'kinase/protein kinase B (Akt), signal transducer and activator of transcription 3 (Stat3) and 5'monophosphateactivated protein kinase (AMPKα) were studied by western blotting. Apelin was increased in JEG3 compared with in BeWo cells, while APJ was the same in both placenta cell lines. Immunocytochemical analyses revealed high cytoplasmic and/or membrane apelin localisation in JEG3, while BeWo cells exhibited markedly weaker apelin signal in the cytoplasm. Apelin increased cell proliferation as well as the percentage of cells in the G2/M phase of the cell cycle, cyclin proteins and the expression of all kinases mentioned above. In conclusion, apelin by promotion of trophoblast cell proliferation by APJ and ERK1/2, Stat3 and AMPKα signalling could be a new important adipokine in the regulation of early placental development.
Asunto(s)
Receptores de Apelina/metabolismo , Apelina/metabolismo , Proliferación Celular/fisiología , Placenta/metabolismo , Transducción de Señal/fisiología , Apelina/análisis , Apelina/genética , Receptores de Apelina/análisis , Receptores de Apelina/genética , Ciclo Celular/fisiología , Femenino , Humanos , Placenta/química , Embarazo , Trofoblastos/metabolismoRESUMEN
BACKGROUND/AIM: apelin and apelin receptor (APJR) are involved in the regulation of angiogenesis, and their high expression is related to poor outcomes in several cancer types. Recently, several positive results on APJR antagonists in cancer treatment have been reported at the preclinical level. The aim of this study was to evaluate the prognostic effect of APJR expression on hepatocellular carcinoma (HCC) survival. MATERIALS AND METHODS: We evaluated APJR expression in 288 curatively resected HCCs using immunohistochemistry and investigated the correlation with clinicopathological features. RESULTS: High APJR expression was significantly associated with the presence of microvascular invasion (p<0.001), intrahepatic metastasis (p=0.004), and early recurrence (p=0.029). The high-expression group showed shorter recurrence-free survival (p<0.001) and overall survival (p=0.001) than the low-expression group. In multivariate analysis, high APJR expression was an independent predictor of shorter recurrence-free survival (Hazard Ratio 1.49; 95% confidence interval 1.08-2.05, p=0.016). CONCLUSION: We described-high APJR expression and its prognostic effect in HCC. Emerging target agents may be applicable in patients with HCC and high APJR expression.