Grewal Thomas, Tews Hauke Christian, Buechler Christa
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.
Department of Internal Medicine I, University Hospital Regensburg, 93053 Regensburg, Germany.
Int J Mol Sci. 2025 Jun 25;26(13):6101. doi: 10.3390/ijms26136101.
Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are related diseases with poorly understood pathophysiology. While therapy options for IBD have increased, treatment options for PSC remain limited. Galectin-3 is a multifunctional lectin expressed in intestinal epithelial cells, and is abundant in immune cells such as macrophages, with roles in cell adhesion, apoptosis, inflammation and fibrosis being associated with IBD and PSC disease development and progression. In addition, galectin-3 is also a visceral fat-derived protein whose systemic levels are increased in obese individuals, the latter correlating with a poorer prognosis in IBD and PSC patients. On the other hand, decreased galectin-3 expression in the inflamed mucosal tissues of mice and patients with IBD possibly indicate a protective role of this lectin in IBD. However, galectin-3 loss or inhibition is protective in most animal models of liver fibrosis but exacerbates the severity of autoimmune liver disease. Hence, with PSC being a slowly progressing autoimmune hepatobiliary disease closely related to IBD, further studies evaluating galectin-3 as a therapeutic target or biomarker for the severity of IBD and the occurrence of PSC are still needed. This review summarizes studies that have analyzed expression patterns and functions of galectin-3 in IBD and PSC. Current evidence suggests that strategies to block galectin-3 are not advised for patients with IBD and PSC-IBD.
炎症性肠病（IBD）和原发性硬化性胆管炎（PSC）是相关疾病，其病理生理学尚不清楚。虽然IBD的治疗选择有所增加，但PSC的治疗选择仍然有限。半乳糖凝集素-3是一种在肠上皮细胞中表达的多功能凝集素，在巨噬细胞等免疫细胞中含量丰富，其在细胞黏附、凋亡、炎症和纤维化方面的作用与IBD和PSC疾病的发生发展相关。此外，半乳糖凝集素-3也是一种源自内脏脂肪的蛋白质，肥胖个体的全身水平会升高，后者与IBD和PSC患者的预后较差相关。另一方面，在IBD小鼠和患者的炎症黏膜组织中半乳糖凝集素-3表达降低，这可能表明该凝集素在IBD中具有保护作用。然而，在大多数肝纤维化动物模型中，半乳糖凝集素-3的缺失或抑制具有保护作用，但会加剧自身免疫性肝病的严重程度。因此，由于PSC是一种与IBD密切相关的缓慢进展的自身免疫性肝胆疾病，仍需要进一步研究评估半乳糖凝集素-3作为IBD严重程度和PSC发生的治疗靶点或生物标志物。本综述总结了分析半乳糖凝集素-3在IBD和PSC中的表达模式和功能的研究。目前的证据表明，不建议对IBD和PSC-IBD患者采用阻断半乳糖凝集素-3的策略。
