👤 Hidehiro Umehara

Diabetes is known to delay wound healing, and this delay is attributed to prolonged inflammation. We found that microRNAs (miRNAs) might be involved in the dysfunction of diabetic-derived neutrophils, and dynamics of neutrophil and chronic inflammation might be initiated by miRNA-regulated genes. Moreover, studies of miRNA function in nephropathy have suggested that circular RNAs (circRNAs), which function as sponges of miRNA to regulate their expression, are potential biomarkers and new therapeutic targets for the diagnosis of diabetic nephropathy. Accordingly, to investigate the molecular mechanism of the regulation of inflammation in diabetic-derived neutrophils, we identified circRNAs in diabetic-derived neutrophils obtained from BKS.Cg- Show less

Because intractable itch reduces quality of life, understanding the fundamental mechanisms of itch is required to develop antipruritic treatments. Itch is mediated by peripheral sensory neurons, which originate from the neural crest (NC) during development. Itch-associated signaling molecules have been detected in genetically engineered animals and in cultures of peripheral neurons from dorsal root ganglia (DRG). Ethical difficulties collecting peripheral neurons from human DRG have limited analysis of itch in humans. This study describes a method of differentiating peripheral neurons from human induced pluripotent stem cells (hiPSCs) for physiological study of itch. This method resulted in the robust induction of p75 and HNK1 double-positive NC cells from hiPSCs. The expression of NC markers TFAP2A, SOX10 and SNAI1 increased during NC induction. The induction efficiency was nearly 90%, and human peripheral neurons expressing peripherin were efficiently differentiated from hiPSC-derived NC cells. Moreover, induced peripheral neurons expressed the sensory neuronal marker BRN3A and the itch-related receptors HRH1, MRGPRX1, IL31R and IL-4R. Calcium imaging analyses indicated that these peripheral neurons included sensory neurons responsive to itch-related stimuli such as histamine, BAM8-22, IL-31 and IL-4. These findings may enable detailed analyses of human DRG neurons and may result in new therapies for intractable itch. Show less

Previous studies suggest that elevated total homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which correlates with plasma total homocysteine levels, are risk factors for schizophrenia (SCZ). Recently, a large genome-wide association study (GWAS) of plasma total homocysteine levels in individuals of European ancestry identified many single-nucleotide polymorphisms (SNPs) (n=13,974). The primary purpose of this study was to examine the association between these plasma total homocysteine-related SNPs and SCZ in the Japanese population. First, we investigated associations between six SNPs and plasma total homocysteine levels in non-psychiatric subjects in the Japanese population (n=1030). Then, we evaluated the cumulative effects of three SNPs on SCZ risk by calculating the Genotype Risk Score (GRS) (1120 cases, 2643 controls). Of the six SNPs examined, we replicated similar associations with the European GWAS at four loci (CENPQ, CPS1, MTHFR, and MUT). GRS based on three SNPs (CENPQ, CPS1, and MTHFR) was significantly associated with SCZ. Our findings suggest that common polygenic variations, which are associated with the plasma total homocysteine levels, may contribute to the risk of SCZ. Show less