Browsing by Author "Lu, Yuan"

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    Alterations in microRNA expression profiles in inflamed and non-inflamed ascending colon mucosae of patients with active Crohn's disease
    (Wiley, 2017) Wu, Lu Yi; Ma, Xiao Peng; Shi, Yin; Bao, Chun Hui; Jin, Xiao Ming; Lu, Yuan; Zhao, Ji Meng; Zhou, Ci Li; Chen, Dai; Liu, Hui Rong; Department of Anatomy & Cell Biology, IU School of Medicine
    Background and aims The miRNA expression profiles of the terminal ileum, sigmoid colon, and rectal mucosa of adult patients with active Crohn';s disease (CD) have been previously reported. The purpose of this study was to identify dysregulated miRNAs in the mucosa of the ascending colon. Methods Biopsy tissue samples were taken from the mucosae of inflammatory (iCD) or non-inflammatory (niCD) areas of the ascending colons of adult patients with active CD. miRNA and mRNA expression profiles were detected using microarray analyses. miRNAs and mRNAs demonstrating significant differences were validated via quantitative real-time PCR (qRT-PCR). Luciferase reporter genes were used to measure two miRNAs inhibition of potential target genes in human 293T cells in vitro. Results Compared with the HC group, the ascending colon miRNA expression profiles revealed that 43 miRNAs were significantly up-regulated and 35 were down-regulated in the iCD group. The mRNA expression profiles indicated that 3,370 transcripts were significantly differentially expressed in the ascending colon, with 2169 up-regulated and 1201 down-regulated mRNAs in the iCD group, and only 20 miRNAs demonstrated significant differential expression in the niCD group. In contrast, nearly 100 miRNAs significantly varied between the iCD and niCD groups. Finally, luciferase reporter gene assays showed that hsa-miR-16-1 directly regulated the human C10orf54 gene and that they were negatively correlated. Conclusions Our results indicated that the differentially expressed miRNAs and mRNAs were related to immune inflammation and intestinal flora. The data provide preliminary evidence that the occurrence of CD involves the inhibition of C10orf54 expression by hsa-miR-16-1.
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    Loss of F-box only protein 2 (Fbxo2) disrupts levels and localization of select NMDA receptor subunits, and promotes aberrant synaptic connectivity
    (Society for Neuroscience, 2015-04-15) Atkin, Graham; Moore, Shannon; Lu, Yuan; Nelson, Rick F.; Tipper, Nathan; Rajpal, Guatam; Hunt, Jack; Tennant, William; Hell, Johannes W.; Murphy, Geoffrey G.; Paulson, Henry; Department of Otolaryngology -- Head & Neck Surgery, IU School of Medicine
    NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these receptors are highly regulated with respect to their localization, activation, and abundance both within and on the surface of mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models and F-box Only Protein 2 (Fbxo2) knock-out mice, we found that the ubiquitin ligase substrate adaptor protein Fbxo2, previously reported to facilitate the degradation of the NMDAR subunit GluN1 in vitro, also functions to regulate GluN1 and GluN2A subunit levels in the adult mouse brain. In contrast, GluN2B subunit levels are not affected by the loss of Fbxo2. The loss of Fbxo2 results in greater surface localization of GluN1 and GluN2A, together with increases in the synaptic markers PSD-95 and Vglut1. These synaptic changes do not manifest as neurophysiological differences or alterations in dendritic spine density in Fbxo2 knock-out mice, but result instead in increased axo-dendritic shaft synapses. Together, these findings suggest that Fbxo2 controls the abundance and localization of specific NMDAR subunits in the brain and may influence synapse formation and maintenance.