ABSTRACT
Abstract Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire on ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes, and cleavage-stage embryos, and the expression level of Lin28 is correlated with the expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of ES cells through a specific pathway (i.e., the activation of Lin28 and the inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms behind the establishment and sustenance of pluripotent identity.
Subject(s)
Cell Proliferation , Embryonic Stem Cells/physiology , RNA-Binding Proteins/metabolism , Transcription Factors/physiology , Animals , Cell Line , Coculture Techniques , Embryo, Mammalian/metabolism , Embryonic Stem Cells/metabolism , Female , Gene Expression , Germ Cells/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Knockout , MicroRNAs/genetics , MicroRNAs/metabolism , Organ Specificity , RNA-Binding Proteins/genetics , Real-Time Polymerase Chain Reaction , Transcription Factors/genetics , Transcription Factors/metabolism , Transcriptional Activation , AIRE ProteinABSTRACT
<p><b>BACKGROUND</b>To study the significance of the expression of HCV core protein in PBMC of patients with chronic hepatitis C and to evaluate the relationship between HCV core protein expression and clinical states.</p><p><b>METHODS</b>Identification of HCV protein antigen (Ag) in PBMC of 66 hepatitis C patients by immunohistochemical method and clinical status of the patients with HCV protein positive expression were investigated. In 27 out off 66 patients the HCV RNA and HCV Ag in PBMC were detected with RT-PCR and immunohistochemical method.</p><p><b>RESULTS</b>The HCV Ag (core+NS3) was identified in PBMC in 51 out of 66 patients (77.27%). It was also demonstrated that HCV core protein in nucleus showed strong expression and NS3 protein in cytoplasm showed weak expression. The expression of core protein in nucleus of PBMC were 35.29% in advanced chronic hepatitis patients, which was significantly higher than that from moderate cases (5.88%).</p><p><b>CONCLUSIONS</b>This study suggested that the expression of PMBC-HCV core protein may be related to the clinical state of the patients. The nuclear expression of HCV core protein in PBMC of patients with hepatitis C may be related to the persistence and activity of the chronic hepatitis C virus and play an important role in the pathogenesis of cirrhrosis and hepatocellular carcinoma.</p>
