Feng Aiwen, Su Shaosheng, Li Qian, Li Cheng, Liu Yingyan, Qiu Jiasheng
The First Clinical Medical College, Guangdong Medical University, China; Department I of Gastrointestinal Surgery, Affiliated Maoming Hospital, Southern Medical University, China; Department I of Gastrointestinal Surgery, Maoming People's Hospital, Maoming City, China.
The First Clinical Medical College, Guangdong Medical University, China.
J Steroid Biochem Mol Biol. 2025 Mar;247:106655. doi: 10.1016/j.jsbmb.2024.106655. Epub 2024 Dec 6.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), affects enteric glial cells (EGCs) activity, but the mechanism is still unknown. The current study aimed to explore whether 1,25(OH)2D3 could regulate EGCs activity via butyrate pathway in a high-fat diet model. Male C57BL/6 J mice were fed with standard diet (SDD), or vitamin-D-deficient diet (VDD), or high-fat diet (HFD), or HFD plus sodium butyrate (SBR), or HFD plus 1,25(OH)2D3, or HFD plus S100B inhibitor ONO-2506 in vivo. CRL-2690 and Caco-2 cells were treated with palmitic acid (PA) and oleic acid (OA) complex, or S100B, or S100B plus butyric acid (BA) in vitro. 25(OH)D3, 1,25(OH)2D3, TNF-α and S100B concentrations were assayed by enzyme-linked immuno- sorbent assay (ELISA). Colonic mucosal permeability was measured by using FITC-dextran 4 kDa. Colonic butyrate was detected using high-performance liquid chromatography (HPLC). The results showed HFD decreased serum 25(OH)D3 and 1,25(OH)2D3 concentrations and colonic butyrate generation. 1,25(OH)2D3 supplementation raised butyrate production in the colon. 1,25(OH)2D3 and sodium butyrate supplementation inhibited EGCs to produce S100B and reduced colonic permeability to FITC-dextran. Inhibition of S100B pathway by ONO- 2506 decreased colonic hyperpermeability. In vitro experiments showed butyrate treatment not only reduced S100B and TNF-α secretion from PA/OA-treated CRL-2690 cells, but also decreased the permeability of S100B-treated Caco-2 cells. Collectively, 1,25(OH)2D3 elicited butyrate to suppress EGCs activation, which helped to prevent intestinal barrier injury.
1,25 - 二羟基维生素D3（1,25(OH)2D3）会影响肠胶质细胞（EGCs）的活性，但其机制尚不清楚。当前研究旨在探讨在高脂饮食模型中，1,25(OH)2D3是否能通过丁酸盐途径调节EGCs的活性。在体内，将雄性C57BL/6 J小鼠分为标准饮食组（SDD）、维生素D缺乏饮食组（VDD）、高脂饮食组（HFD）、高脂饮食加丁酸钠组（SBR）、高脂饮食加1,25(OH)2D3组、高脂饮食加S100B抑制剂ONO - 2506组进行喂养。在体外，用棕榈酸（PA）和油酸（OA）复合物、S100B或S100B加丁酸（BA）处理CRL - 2690和Caco - 2细胞。采用酶联免疫吸附测定法（ELISA）检测25(OH)D3、1,25(OH)2D3、肿瘤坏死因子-α（TNF-α）和S100B的浓度。使用4 kDa异硫氰酸荧光素 - 葡聚糖（FITC - dextran）测量结肠黏膜通透性。采用高效液相色谱法（HPLC）检测结肠丁酸盐。结果显示，高脂饮食降低了血清25(OH)D3和1,25(OH)2D3的浓度以及结肠丁酸盐的生成。补充1,25(OH)2D3可提高结肠中丁酸盐的产生。补充1,25(OH)2D3和丁酸钠可抑制EGCs产生S100B，并降低结肠对FITC - dextran的通透性。ONO - 2506抑制S100B途径可降低结肠高通透性。体外实验表明，丁酸盐处理不仅减少了PA/OA处理的CRL - 2690细胞中S100B和TNF-α的分泌，还降低了S100B处理的Caco - 2细胞通透性。总体而言，1,25(OH)2D3促使丁酸盐抑制EGCs激活，有助于预防肠道屏障损伤。
