Zhang Kun, Xu Lingfen, Guo Jing
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
Pediatr Res. 2024 Nov 1. doi: 10.1038/s41390-024-03640-3.
In this study, we aimed to explore the role of Tarm1 in juvenile mice with dextran sulfate sodium (DSS)-induced colitis and elucidate the mechanisms that affect intestinal barrier function.
A DSS-induced pediatric inflammatory bowel disease mouse model was established using 4-week-old juvenile mice. Disease activity index and histopathological damage scores were determined using hematoxylin and eosin (H&E) staining. Tarm1, F4/80, CD68, and CD86 levels were detected using qPCR, western blotting, and immunofluorescence. Trans epithelial electric resistance (TEER) was detected using the transwell assay.
Results revealed that juvenile colitis mice fed 4% DSS drinking water had increased Tarm1 expression in the colon tissue, increased macrophage M1 polarization, higher expression of pro-inflammatory cytokines, and an impaired intestinal mucosal barrier, compared with the control group. Tarm1-knockdown RAW264.7 cells inhibited lipopolysaccharide (LPS)-induced M1 polarization and attenuated barrier damage in co-cultured intestinal epithelial cells.
Tarm1 expression was increased in colonic tissues of juvenile mice with colitis, and LPS-induced M1 polarization and intestinal barrier damage were attenuated in Tarm1-knockdown RAW264.7 cells. This suggests that attenuation of Tarm1 expression is a potential target for pediatric inflammatory bowel disease therapy.
在本研究中，我们旨在探讨Tarm1在葡聚糖硫酸钠（DSS）诱导的幼年小鼠结肠炎中的作用，并阐明影响肠道屏障功能的机制。
使用4周龄的幼年小鼠建立DSS诱导的儿童炎症性肠病小鼠模型。使用苏木精和伊红（H&E）染色确定疾病活动指数和组织病理学损伤评分。使用qPCR､蛋白质免疫印迹法和免疫荧光检测Tarm1､F4/80､CD68和CD86水平。使用transwell实验检测跨上皮电阻（TEER）。
结果显示，与对照组相比，饮用4%DSS饮用水的幼年结肠炎小鼠结肠组织中Tarm1表达增加，巨噬细胞M1极化增加，促炎细胞因子表达更高，肠黏膜屏障受损。Tarm1基因敲低的RAW264.7细胞抑制脂多糖（LPS）诱导的M1极化，并减轻共培养的肠上皮细胞中的屏障损伤。
结肠炎幼年小鼠结肠组织中Tarm1表达增加，Tarm1基因敲低的RAW264.7细胞中LPS诱导的M1极化和肠屏障损伤减弱。这表明降低Tarm1表达是儿童炎症性肠病治疗的潜在靶点。
