通过抑制 S100B/ADAM10 通路补充 1,25(OH)2D3，减轻肠道血管屏障的破坏。

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Tissue Barriers Pub Date : 2024-03-17 DOI:10.1080/21688370.2024.2327776

Aiwen Feng, Cheng Li, Shaosheng Su, Yingyan Liu

{"title":"通过抑制 S100B/ADAM10 通路补充 1,25(OH)2D3，减轻肠道血管屏障的破坏。","authors":"Aiwen Feng, Cheng Li, Shaosheng Su, Yingyan Liu","doi":"10.1080/21688370.2024.2327776","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"1,25(OH)2D3 supplementation alleviates gut-vascular barrier disruption via inhibition of S100B/ADAM10 pathway.\",\"authors\":\"Aiwen Feng, Cheng Li, Shaosheng Su, Yingyan Liu\",\"doi\":\"10.1080/21688370.2024.2327776\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":23469,\"journal\":{\"name\":\"Tissue Barriers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tissue Barriers\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/21688370.2024.2327776\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue Barriers","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21688370.2024.2327776","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

摘要

肠道-血管屏障（GVB）是黏膜上控制肠道细菌全身传播的第二道屏障。严重烧伤会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。目前尚不清楚补充维生素 D3 是否能通过调节 S100B/ADAM10 途径减轻 GVB 损伤。在这里，GVB破坏是由总体表面积30%的烫伤诱发的。大鼠接受 1,25（OH）2D3（0.05、0.5 或 5 μg/kg）或 S100B 单克隆抗体（S100BmAb，10 μg/kg）或 GI254023X（ADAM10 抑制剂，100 mg/kg）治疗。大鼠肠胶质细胞系 CRL2690 和大鼠肠微血管内皮细胞（RIMECs）用 S100B（5 μM）或加 1,25(OH)2D3（0.05、0.5 或 5 μM）或 GI254023X（5 μM）处理。血清和肠道粘膜中的 S100B、TNF-α、25(OH)D3 和 1,25(OH)2D3 用酶联免疫吸附法测定。使用 FITC-dextran 70 kDa 测量内皮通透性。用 Western 印迹法测定 ADAM10 和 β-catenin 的表达。结果显示，烧伤大鼠血清中的 1,25(OH)2D3 和 25(OH)D3 浓度降低，而血清和肠道粘膜中的 TNF-α 和 S100B 浓度升高。S100BmAb、GI254023X 和 1,25（OH）2D3 治疗可降低烧伤后增加的 GVB 通透性。1,25(OH)2D3 还能降低血清和肠道粘膜中的 S100B 浓度。1,25(OH)2D3 可抑制 TNF-α 处理的 CRL2690 中 S100B 的释放，并在 S100B 处理的 RIMECs 中提高 β-catenin，同时降低 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，这些发现提供了严重烧伤会降低血清 25(OH)D3 和 1,25(OH)2D3 浓度的证据。补充 1,25(OH)2D3可通过抑制 S100B/ADAM10 信号转导减轻烧伤引起的 GVB 破坏。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

1,25(OH)2D3 supplementation alleviates gut-vascular barrier disruption via inhibition of S100B/ADAM10 pathway.

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.60

自引率

6.50%

发文量

期刊介绍： Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.