金属蛋白酶在炎症性肠病和结肠癌病理生理中的作用。

IF 3.1 3区 医学 Q3 CELL BIOLOGY
Laura D Manzanares, Caroline J Herrnreiter, Joseph Hirst, Ronen Sumagin
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引用次数: 0

摘要

炎症性肠病(IBD)是一种使人衰弱且有症状的胃肠道疾病,以炎症失调、肠道损伤和屏障功能障碍为特征。IBD也是结直肠癌(CRC)的危险因素,结直肠癌仍然是全球癌症相关死亡的主要原因。基质金属蛋白酶(MMPs)是一个多样化的蛋白酶家族,在肠道内稳态和疾病发病机制中发挥关键作用。MMPs由上皮细胞、基质细胞和免疫细胞产生,可以通过细胞外基质重塑、细胞因子激活或与靶细胞直接相互作用调节干细胞功能、免疫细胞募集、微生物组成、屏障完整性、血管生成和细胞增殖,从而影响IBD和CRC的进展。在这篇综述中,我们讨论了MMPs在维持肠道稳态中的作用,以及它们在IBD中不平衡的免疫反应、上皮完整性和伤口愈合中的作用。此外,我们强调了它们在结直肠癌的上皮到间质转化、血管生成和转移中的作用。最后,我们回顾了MMPs作为IBD/CRC诊断、预后和治疗反应的生物标志物的潜在应用。MMPs仍然是IBD和CRC生物学的核心,为治疗干预和疾病监测带来了挑战和机遇。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The function of metalloproteinases in pathophysiology of inflammatory bowel disease and colon cancer.

Inflammatory bowel disease (IBD) is a debilitating and symptomatic disorder of the gastrointestinal tract, featuring dysregulated inflammation, intestinal injury, and barrier dysfunction. IBD is also a risk factor for colorectal cancer (CRC), which remains a leading cause of cancer-related mortalities worldwide. Matrix metalloproteinases (MMPs) are a diverse family of proteases that play critical roles in both intestinal homeostasis and disease pathogenesis. Produced by epithelial, stromal, and immune cells, MMPs can regulate stem cell function, immune cell recruitment, microbial composition, barrier integrity, angiogenesis, and cell proliferation through extracellular matrix remodeling, cytokine activation, or direct interactions with target cells, thereby impacting the progression of both IBD and CRC. In this review we discuss the roles of MMPs in the maintenance of intestinal homeostasis and their contributions to imbalanced immune responses, epithelial integrity, and wound healing in IBD. Additionally, we highlight their contribution to epithelial-to-mesenchymal transition, angiogenesis, and metastasis in CRC. Finally, we review the potential utilization of MMPs as biomarkers for IBD/CRC diagnosis, prognosis, and treatment response. MMPs remain central to both IBD and CRC biology and present both challenges and opportunities for therapeutic intervention and disease monitoring.

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来源期刊
Journal of Leukocyte Biology
Journal of Leukocyte Biology 医学-免疫学
CiteScore
11.50
自引率
0.00%
发文量
358
审稿时长
2 months
期刊介绍: JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.
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