丁酸钠调节 Gasdermin B 对 MTX 诱导的 NCM460 和 Hum 细胞的保护作用,Advanced Therapeutics

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丁酸钠调节 Gasdermin B 对 MTX 诱导的 NCM460 和 Hum 细胞的保护作用
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2023-11-03 , DOI: 10.1002/adtp.202300328
Chensheng Jiang ₁ , Yang Liu ₂ , Hangping Chen ₃ , Yifan Qian ₄ , Leilei Tang ₃ , Channi Wu ₅ , Tiemei Han ₁ , Chengfeng Jin ₁ , Haihong Ju ₆ , Xiaofeng Shen ₆ , Jiawen Yu ₃ , Lingdi Zhang ₃ , Yiyang Dai ₁ , Guojun Jiang ₃

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炎症性肠病（IBD）是一种病因不明的复杂疾病，短链脂肪酸（SCFA）对其发病机制的影响尚未得到充分研究。本研究探讨了丁酸钠 (NaB) 通过 Gasdermin B (GSDMB) 非焦亡途径对炎症性肠病 (IBD) 的潜在保护作用。分析 IBD 患者粪便 SCFA 水平和 GSDMB 相关蛋白。 NCM460 和 HUM 细胞用甲氨蝶呤 (MTX) 处理 24 小时。将NaB以1、5和10 m m mL ^-1的浓度施加至细胞。研究发现 IBD 患者中 SCFAs 含量、小带 occlusionns-1 (ZO-1) 和 Occludin 表达减少，而 GSDMB、粘着斑激酶 (FAK) 和细胞外信号调节激酶 (ERK) 增加被观察到。中浓度和高浓度的 NaB 可促进细胞活力和迁移并增加 GSDMB 表达。低浓度的NaB对IBD受影响的细胞具有显着的保护作用，激活GSDMB非焦亡途径。 GSDMB 敲低后，这种保护作用就会减弱。研究表明，NaB 可能通过 GSDMB 非焦亡途径在保护 IBD 肠上皮完整性方面发挥关键作用。这些发现强调了针对该途径的治疗策略的潜力，强调了 SCFA 在理解和治疗 IBD 中的重要性。

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Sodium Butyrate Regulates Gasdermin B Exerted Protection Effect on the MTX-Induced NCM460 and Hum Cells

Inflammatory bowel disease (IBD) is a complex disorder with unclear etiology, and the impact of short-chain fatty acids (SCFAs) on its pathogenesis is not well-studied. This research explores the potential protective effects of sodium butyrate (NaB) in inflammatory bowel disease (IBD) through the Gasdermin B (GSDMB) non-pyroptotic pathway. Fecal SCFA levels and GSDMB-related proteins of IBD patients are analyzed. NCM460 and HUM cells are treated with methotrexate (MTX) for 24 hours. NaB is applied at concentrations of 1, 5, and 10 mm mL⁻¹ to cells. It is found that a decrease in SCFAs content, zonula occludens-1 (ZO-1), and Occludin expression, along with an increase in GSDMB, focal adhesion kinase (FAK), and extracellular singal-regulated kinase (ERK) in IBD patients is observed. NaB, at medium and high concentrations, promotes cell viability and migration and increased GSDMB expression. The low concentration of NaB has a significant protective effect on IBD-affected cells, activating the GSDMB non-pyroptotic pathway. This protection diminishes after the GSDMB knockdown. The study reveals that NaB may play a crucial role in protecting intestinal epithelial integrity in IBD through the GSDMB non-pyroptotic pathway. These findings underline the potential of targeting this pathway for therapeutic strategies, highlighting the importance of SCFAs in understanding and treating IBD.

更新日期：2023-11-03

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