ABSTRACT
BACKGROUND: After encountering COVID-19 patients who test positive again after discharge, our study analyzed the pathogenesis to further assess the risk and possibility of virus reactivation. METHODS: A separate microarray was acquired from the Gene Expression Omnibus (GEO), and its samples were divided into two groups: a "convalescent-RTP" group consisting of convalescent and "retesting positive" (RTP) patients (group CR) and a "healthy-RTP" group consisting of healthy control and RTP patients (group HR). The enrichment analysis was performed with R software, obtaining the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the protein-protein interaction (PPI) networks of each group were established, and the hub genes were discovered using the cytoHubba plugin. RESULTS: In this study, 6622 differentially expressed genes were identified in the group CR, among which RAB11B-AS1, DISP1, MICAL3, PSMG1, and DOCK4 were up-regulated genes, and ANAPC1, IGLV1-40, SORT1, PLPPR2, and ATP1A1-AS1 were down-regulated. 7335 genes were screened in the group HR, including the top 5 up-regulated genes ALKBH6, AMBRA1, MIR1249, TRAV18, and LRRC69, and the top 5 down-regulated genes FAM241B, AC018529.3, AL031963.3, AC006946.1, and FAM149B1. The GO and KEGG analysis of the two groups revealed a significant enrichment in immune response and apoptosis. In the PPI network constructed, group CR and group HR identified 10 genes, respectively, and TP53BP1, SNRPD1, and SNRPD2 were selected as hub genes. CONCLUSIONS: Using the messenger ribonucleic acid (mRNA) expression data from GSE166253, we found TP53BP1, SNRPD1, and SNRPD2 as hub genes in RTP patients, which is vital to the management and prognostic prediction of RTP patients.
Subject(s)
COVID-19 , Computational Biology , COVID-19/diagnosis , COVID-19/genetics , COVID-19 Testing , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks/genetics , Humans , Patient Discharge , RecurrenceABSTRACT
Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL-33 significantly prolonged islet allograft survival. IL-33-treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL-33 on allograft survival, and additional ILC2 depletion in Treg-depleted DEREG mice completely abolished the protective effects of IL-33, indicating that ILC2s play critical roles in IL-33-mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL-33-treated mice: IL-10 producing ILC2s (ILC210 ) and non-IL-10 producing ILC2s (non-ILC10 ). Intravenous transfer of ILC210 cells, but not non-ILC10 , prolonged islet allograft survival in an IL-10-dependent manner. Locally transferred ILC210 cells led to long-term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.
Subject(s)
Immunity, Innate , Lymphocytes , Allografts , Animals , Interleukin-10 , Mice , T-Lymphocytes, RegulatoryABSTRACT
[This corrects the article DOI: 10.3892/etm.2019.7840.].
ABSTRACT
Caveolin-3 (CAV3) is a muscle-specific protein present within the muscle cell membrane that affects signaling pathways, including the insulin signaling pathway. A previous assessment of patients with newly developed type 2 diabetes (T2DM) demonstrated that CAV3 gene mutations may lead to changes in protein secondary structure. A severe CAV3 P104L mutation has previously been indicated to influence the phosphorylation of skeletal muscle cells and result in impaired glucose metabolism. In the present study, the effect of CAV3 K15N gene transfection in C2C12 cells was assessed. Transfection with K15N reduced the expression of total CAV3 and AKT2 proteins in the cells, and the translocation of glucose transporter type 4 to the muscle cell membrane, which resulted in decreased glucose uptake and glycogen synthesis in myocytes. In conclusion, these results indicate that the CAV3 K15N mutation may cause insulin-stimulated impaired glucose metabolism in myocytes, which may contribute to the development of T2DM.
ABSTRACT
The caveolin-3 (CAV3) protein is known to be specifically expressed in various myocytes, and skeletal muscle consumes most of the blood glucose as an energy source to maintain normal cell metabolism and function. The P104L mutation in the coding sequence of the human CAV3 gene leads to autosomal dominant disease limb-girdle muscular dystrophy type 1C (LGMD-1C). We previously reported that C2C12 cells transiently transfected with the P104L CAV3 mutant exhibited decreased glucose uptake and glycogen synthesis after insulin stimulation. The present study aimed to examine whether the P104L mutation affects C2C12 cell glucose metabolism, growth, and proliferation without insulin stimulation. C2C12 cells stably transfected with CAV3-P104L were established, and biochemical assays, western blot analysis and confocal microscopy were used to observe glucose metabolism as well as cell growth and proliferation and to determine the effect of the P104L mutation on the PI3K/Akt signaling pathway. Without insulin stimulation, C2C12 cells stably transfected with the P104L CAV3 mutant exhibited decreased glucose uptake and glycogen synthesis, decreased CAV3 expression and reduced localization of CAV3 and GLUT4 on the cell membrane. The P104L mutant significantly reduced the cell diameters, but accelerated cell proliferation. Akt phosphorylation was inhibited, and protein expression of GLUT4, p-GSK3ß, and p-p70s6K, which are molecules downstream of Akt, was significantly decreased. The CAV3-P104L mutation inhibits glycometabolism and cell growth but accelerates C2C12 cell proliferation by reducing CAV3 protein expression and cell membrane localization, which may contribute to the pathogenesis of LGMD-1C.
