Fonseca-Camarillo Gabriela, Furuzawa-Carballeda Janette, Miguel-Cruz Erika, Barreto-Zuñiga Rafel, Martínez-Benítez Braulio, Yamamoto-Furusho Jesus K
Inflammatory Bowel Disease Clinic, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Vasco de Quiroga #15, Col. Belisario Domínguez Sección XVI, 14080, Mexico City, CPCDMX, Mexico.
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, México.
Immunol Res. 2025 Jan 14;73(1):33. doi: 10.1007/s12026-024-09583-5.
The ABCC subfamily contains thirteen members. Nine of these transporters are called multidrug resistance proteins (MRPs). The MRPs have been associated with developing ulcerative colitis (UC). This study aimed to evaluate the ABCC expression in UC patients and its role in a dextran sulfate sodium (DSS)-induced colitis mice model under 5-aminosalicylates or methylprednisolone treatment and compared with control without inflammation. DSS-induced colitis mice were treated with 5-aminosalicylates (50 mg/kg 24 h) or methylprednisolone (2 mg/kg 24 h). Human rectal biopsies were obtained from UC patients. The abcc-relative mRNA levels and protein expression were determined by RT-PCR and immunohistochemistry. abcc4, abcc5, and abcc6 mRNA levels were significantly increased in DSS-induced colitis compared to the other groups. The 5-aminosalicylate treatment dramatically increased the abcc2 and abcc3 mRNA levels vs. control. Methylprednisolone treatment increased abcc1 vs. DSS-induced colitis and colitis treated with 5-aminosalicylate. Immunohistochemical analysis revealed down-regulation of ABCC1/ABCC2/ABCC5/ABCC7 in mice colitis vs. control. Treatment with 5-aminosalicylate restored ABCC5 levels, while methylprednisolone restored ABCC2/ABCC5/ABCC7 in colitis mice at similar control levels. Relative mRNA levels of mrp1-5 were increased in active UC patients vs. control. ABCC2/ABCC4/ABCC7 were conspicuously expressed in the mucosa of 5-aminosalicylate and/or methylprednisolone-treated UC patients, while ABCC2/ABCC4/ABCC5/ABCC7 in submucosa, ABCC1/ABCC5/ABCC7 in muscular, and ABCC1/ABCC4/ABCC5/ABCC7 in serosa were expressed vs. controls. This is the first report about the differential up-regulation of the ABCC subfamily gene and protein expression in DSS-induced colitis under aminosalicylates or methylprednisolone treatment.
ABCC亚家族包含13个成员。其中9种转运蛋白被称为多药耐药蛋白（MRPs）。这些MRPs与溃疡性结肠炎（UC）的发生有关。本研究旨在评估UC患者中ABCC的表达及其在5-氨基水杨酸或甲基强的松龙治疗下的葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中的作用，并与无炎症的对照组进行比较。DSS诱导的结肠炎小鼠用5-氨基水杨酸（50mg/kg，24小时）或甲基强的松龙（2mg/kg，24小时）治疗。从UC患者获取人直肠活检组织。通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学测定abcc相关的mRNA水平和蛋白表达。与其他组相比，DSS诱导的结肠炎中abcc4、abcc5和abcc6的mRNA水平显著升高。与对照组相比，5-氨基水杨酸治疗显著增加了abcc2和abcc3的mRNA水平。与DSS诱导的结肠炎和用5-氨基水杨酸治疗的结肠炎相比，甲基强的松龙治疗增加了abcc1。免疫组织化学分析显示，与对照组相比，小鼠结肠炎中ABCC1/ABCC2/ABCC5/ABCC7下调。5-氨基水杨酸治疗可恢复ABCC5水平，而甲基强的松龙可将结肠炎小鼠中的ABCC2/ABCC5/ABCC7恢复至与对照组相似的水平。与对照组相比，活动期UC患者中mrp1 - 5的相对mRNA水平升高。ABCC2/ABCC4/ABCC7在5-氨基水杨酸和/或甲基强的松龙治疗的UC患者的黏膜中显著表达，而黏膜下层中的ABCC2/ABCC4/ABCC5/ABCC7、肌层中的ABCC1/ABCC5/ABCC7和浆膜中的ABCC1/ABCC4/ABCC5/ABCC7与对照组相比有表达。这是关于在氨基水杨酸或甲基强的松龙治疗下DSS诱导的结肠炎中ABCC亚家族基因和蛋白表达差异上调的首次报道。
