Department of General Surgery, Maoming People's Hospital, Southern Medical University, Zhanjiang, China.
Department of General Surgery, Maoming People's Hospital, Guangdong Medical University, Guangzhou, China.
Tissue Barriers. 2024 Oct;12(4):2327776. doi: 10.1080/21688370.2024.2327776. Epub 2024 Mar 17.
Gut-vascular barrier (GVB) is the second barrier in mucosa to control systemic dissemination of gut bacteria. Severe burns induce enteroglial cells to produce S100B and endothelial cells to generate ADAM10 and cause vitamin D3 insufficiency/deficiency and GVB disruption. It is not clear whether vitamin D3 supplementation attenuates GVB damage via regulation of S100B/ADAM10 pathway. Here, GVB disruption was induced by 30% of total body surface area scalds. Rats were treated with 1,25(OH)2D3 (0.05, 0.5 or 5 μg/kg) or S100B monoclonal antibody (S100BmAb, 10 μg/kg) or GI254023X (ADAM10 inhibitor, 100 mg/kg). Rat enteric glial cell-line CRL2690 and rat intestinal microvascular endothelial cells (RIMECs) were treated with S100B (5 μM) or plus 1,25(OH)2D3 (0.05, 0.5 or 5 μM) or GI254023X (5 μM). S100B, TNF-α, 25(OH)D3 and 1,25(OH)2D3 in serum and gut mucosa were determined by enzyme-linked immunosorbent assay. The endothelial permeability was measured using FITC-dextran 70 kDa. ADAM10 and β-catenin expression was assayed by Western blot. The results showed that 1,25(OH)2D3 and 25(OH)D3 concentration in serum reduced whereas TNF-α and S100B in serum and gut mucosa increased in burned rats. S100BmAb, GI254023X and 1,25(OH)2D3 treatment lowered burns-increased GVB permeability. 1,25(OH)2D3 also decreased S100B concentration in serum and gut mucosa. 1,25(OH)2D3 inhibited S100B release from TNF-α-treated CRL2690 and raised β-catenin while decreasing ADAM10 protein in S100B-treated RIMECs. 1,25(OH)2D3 and GI254023X also decreased the endothelial permeability of S100B-treated RIMECs. Collectively, these findings provide evidence that severe burns lower serum 25(OH)D3 and 1,25(OH)2D3 concentration. 1,25(OH)2D3 supplementation alleviates burns-elicited GVB disruption via inhibition of S100B/ADAM10 signaling.
肠道血管屏障（GVB）是控制肠道细菌全身传播的黏膜第二道屏障。严重烧伤诱导肠胶质细胞产生 S100B 和内皮细胞产生 ADAM10，导致维生素 D3 不足/缺乏和 GVB 破坏。目前尚不清楚维生素 D3 补充是否通过调节 S100B/ADAM10 通路来减轻 GVB 损伤。在这里，通过 30%的全身体表面积烫伤来诱导 GVB 破坏。用 1,25(OH)2D3（0.05、0.5 或 5μg/kg）或 S100B 单克隆抗体（S100BmAb，10μg/kg）或 GI254023X（ADAM10 抑制剂，100mg/kg）处理大鼠。用 S100B（5μM）或 S100B 加 1,25(OH)2D3（0.05、0.5 或 5μM）或 GI254023X（5μM）处理大鼠肠胶质细胞系 CRL2690 和大鼠肠道微血管内皮细胞（RIMECs）。通过酶联免疫吸附试验测定血清和肠道黏膜中的 S100B、TNF-α、25(OH)D3 和 1,25(OH)2D3。使用 FITC-葡聚糖 70kDa 测量内皮通透性。通过 Western blot 测定 ADAM10 和 β-连环蛋白的表达。结果表明，烧伤大鼠血清中 1,25(OH)2D3 和 25(OH)D3 浓度降低，而血清和肠道黏膜中 TNF-α和 S100B 增加。S100BmAb、GI254023X 和 1,25(OH)2D3 治疗降低了烧伤引起的 GVB 通透性增加。1,25(OH)2D3 还降低了血清和肠道黏膜中的 S100B 浓度。1,25(OH)2D3 抑制 TNF-α处理的 CRL2690 中 S100B 的释放，增加 β-连环蛋白，同时降低 S100B 处理的 RIMECs 中的 ADAM10 蛋白。1,25(OH)2D3 和 GI254023X 还降低了 S100B 处理的 RIMECs 的内皮通透性。总之，这些发现提供了证据表明严重烧伤降低了血清 25(OH)D3 和 1,25(OH)2D3 浓度。1,25(OH)2D3 补充通过抑制 S100B/ADAM10 信号通路减轻烧伤引起的 GVB 破坏。
