{"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":"<p><p>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.</p>","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}
引用次数: 0
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.
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.