Expression-Based Genome-Wide Association Study Links Vitamin D-Binding Protein With Autoantigenicity in Type 1 Diabetes.

Type 1 diabetes (T1D) is caused by autoreactive T cells that recognize pancreatic islet antigens and destroy insulin-producing β-cells. This attack results from a breakdown in tolerance for self-antigens, which is controlled by ectopic antigen expression in the thymus and pancreatic lymph nodes (PLNs). The autoantigens known to be involved include a set of islet proteins, such as insulin, GAD65, IA-2, and ZnT8. In an attempt to identify additional antigenic proteins, we performed an expression-based genome-wide association study using microarray data from 118 arrays of the thymus and PLNs of T1D mice. We ranked all 16,089 protein-coding genes by the likelihood of finding repeated differential expression and the degree of tissue specificity for pancreatic islets. The top autoantigen candidate was vitamin D-binding protein (VDBP). T-cell proliferation assays showed stronger T-cell reactivity to VDBP compared with control stimulations. Higher levels and frequencies of serum anti-VDBP autoantibodies (VDBP-Abs) were identified in patients with T1D (n = 331) than in healthy control subjects (n = 77). Serum vitamin D levels were negatively correlated with VDBP-Ab levels in patients in whom T1D developed during the winter. Immunohistochemical localization revealed that VDBP was specifically expressed in α-cells of pancreatic islets. We propose that VDBP could be an autoantigen in T1D

Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent to treat cancer. Among its many side effects is the well-known consequence on tooth development when administered at early ages. This study elucidated the effects of CPA on development of the mandibular molar in mice. Mice received a single intraperitoneal injection of CPA at different doses and development times. CPA treatment led to weight loss and alopecia but had no effect on disturbances in tooth eruption or crown shape. However, at higher doses, there was arrested root development and early apical foramen closure histologically related to the formation of the cervical loop structure in the apical portion of the root. In cell culture experiments, the Hertwig\u27s epithelial root sheath cell line (HERS01a) was cultured with or without CPA. At high doses of CPA, HERS01a cells showed decreases in E-cadherin expression, while N-cadherin expression was upregulated, indicating that this cadherin switch may promote an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrested root development of the molars and an EMT-like phenomenon.福岡歯科大学2019年

Effects of dietary lard and fish oil on the serum lipid level and aortic tissue : a comparison in quail animal model

A total of twenty-five 40-day-old, male, Japanese quails were fed with either basal diet, a diet containing 15% butter fat and 2% cholesterol, or a diet containing 15% fish oil and 2% cholesterol for 3 months. The birds which were fed with the diet containing lard and cholesterol showed marked hypercholesterolemia and severe lipid-rich aortic lesions. In accordance to serum cholesterol level, the lard fed group had numerous fibroblasts with or without lipid droplets in the thickened intima of the ascending aorta. The birds fed with the fish oil and cholesterol had no significant increase in their serum cholesterol level or lipid-rich aortic lesions. These data clearly indicate that fish oil is less atherogenic than lard

Effects of Fibrillin Application on Periodontal Ligament Regeneration in Mouse Model of Tooth Replantation

福岡歯科大学2015年

Intracellular Signaling Pathway Activation via TGF-β Differs in the Anterior and Posterior Axis During Palatal Development

福岡歯科大学2015年

Transforming growth factor-beta and sonic hedgehog signaling in palatal epithelium regulate tenascin-C expression in palatal mesenchyme during soft palate development.

福岡歯科大学2020年

Cisplatin-Induced Sonic Hedgehog Signaling Mediates Epithelial-Mesenchymal Transition in Hertwig’s Epithelial Root Sheath Cells.

福岡歯科大学2020年