Browsing by Author "Wang, Q."
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Item Dysregulation of RBFOX2 is an Early Event in Cardiac Pathogenesis of Diabetes(Elsevier) Nutter, C. A.; Jaworski, E. A.; Verma, S. K.; Deshmukh, V.; Wang, Q.; Botvinnik, O. B.; Lozano, Mario J.; Abass, I. J.; Ijaz, T.; Brasier, A.; Garg, N.; Wehrens, X.; Yeo, G.; Kuyumcu-Martinez, M.; Lozano, Mario J.Alternative splicing (AS) defects that adversely affect gene expression and function have been identified in diabetic hearts; however, the mechanisms responsible are largely unknown. Here, we show that the RNA-binding protein RBFOX2 contributes to transcriptome changes under diabetic conditions. RBFOX2 controls AS of genes with important roles in heart function relevant to diabetic cardiomyopathy. RBFOX2 protein levels are elevated in diabetic hearts despite low RBFOX2 AS activity. A dominant-negative (DN) isoform of RBFOX2 that blocks RBFOX2-mediated AS is generated in diabetic hearts. DN RBFOX2 interacts with wild-type (WT) RBFOX2, and ectopic expression of DN RBFOX2 inhibits AS of RBFOX2 targets. Notably, DN RBFOX2 expression is specific to diabetes and occurs at early stages before cardiomyopathy symptoms appear. Importantly, DN RBFOX2 expression impairs intracellular calcium release in cardiomyocytes. Our results demonstrate that RBFOX2 dysregulation by DN RBFOX2 is an early pathogenic event in diabetic hearts. Nutter et al. show that the majority of transcripts mis-spliced in diabetic hearts have RBFOX2-binding sites. In diabetic hearts, a DN isoform of RBFOX2 with inhibitory splicing function is generated in response to high protein levels of WT RBFOX2. DN RBFOX2 upregulation occurs before cardiac complications manifest. © 2016 The Author(s).Item Maternal Hyperuricemia Superimposed on Maternal Hypertension Aggravates the Risk of Small-for-Gestational-Age Fetus(Elsevier Inc., 2019-04-16) Liu, L.; Yu, Chunxiao; Yang, F.; Yuan, Z.; Wang, Q.; Liu, S.; Zuo, C.; Guan, Q.; Yu, ChunxiaoAims: Small-for-gestational-age (SGA) fetus is an important public health issue because of its high mortality and long-term effects on health. Maternal hyperuricemia is associated with diverse adverse pregnant outcomes and neonatal disturbance. We aimed to evaluate whether maternal hyper-uric acid (HUA) is associated with the risk of SGA fetus and to explore whether it can modify the association between maternal hyper-blood pressure (HBP) and SGA fetus. Materials and methods: We performed a population-based cross-section retrospective study, a total of 6715 pregnant females were recruited. Multiple logistic regression analysis was performed to identify risk factors significantly correlated with SGA fetus, and then studied the effect of maternal HUA on the association between maternal HBP and SGA fetus. Key findings: We collected 537 SGA fetuses among 6715 pregnant females. Maternal HUA was an independent risk factor for SGA delivery (odds ratio (OR), 2.737; 95% confidence interval (CI), 2.110–3.551). A dose–response association between maternal uric acid and SGA delivery was found among normotensive and hypertensive group. Compared with those whose uric acid was lower than 270 µmo/L with normal–blood pressure (NBP), the risk for SGA delivery in those whose uric acid was higher than 370 µmo/L with stage 2 or 3 hypertension increased 12.695–fold. Significance: Our results suggest that maternal HUA could increase the risk of neonatal SGA, and maternal HUA could be superimposed upon pre-existing maternal HBP and increase the risk for SGA fetus. © 2019 The Authors