Department of Pathology, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
Department of Surgery, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
Cells. 2024 Jul 11;13(14):1178. doi: 10.3390/cells13141178.
Thousands struggle with acute and chronic intestinal injury due to various causes. Epithelial intestinal healing is dependent on phenotypic transitions to a mobile phenotype. Focal adhesion kinase (FAK) is a ubiquitous protein that is essential for cell mobility. This phenotype change is mediated by FAK activation and proves to be a promising target for pharmaceutical intervention. While FAK is crucial for intestinal healing, new evidence connects FAK with innate immunity and the importance it plays in macrophage/monocyte chemotaxis, as well as other intracellular signaling cascades. These cascades play a part in macrophage/monocyte polarization, maturation, and inflammation that is associated with intestinal injury. Colony stimulating factors (CSFs) such as macrophage colony stimulating factor (M-CSF/CSF-1) and granulocyte macrophage colony stimulating factor (GM-CSF/CSF-2) play a critical role in maintaining homeostasis within intestinal mucosa by crosstalk capabilities between macrophages and epithelial cells. The communication between these cells is imperative in orchestrating healing upon injury. Diving deeper into these connections may allow us a greater insight into the role that our immune system plays in healing, as well as a better comprehension of inflammatory diseases of the gut.
由于各种原因,成千上万的人患有急性和慢性肠损伤。肠上皮的愈合依赖于向移动表型的表型转变。粘着斑激酶(FAK)是一种普遍存在的蛋白质,对细胞迁移至关重要。这种表型变化是由 FAK 激活介导的,被证明是药物干预的一个有前途的靶点。虽然 FAK 对肠道愈合至关重要,但新的证据将 FAK 与先天免疫联系起来,并证明它在巨噬细胞/单核细胞趋化作用以及其他细胞内信号级联中起着重要作用。这些级联在与肠道损伤相关的巨噬细胞/单核细胞极化、成熟和炎症中发挥作用。集落刺激因子(CSFs),如巨噬细胞集落刺激因子(M-CSF/CSF-1)和粒细胞巨噬细胞集落刺激因子(GM-CSF/CSF-2),通过巨噬细胞和上皮细胞之间的串扰能力,在维持肠道黏膜内的稳态方面发挥着关键作用。这些细胞之间的通讯对于协调损伤后的愈合至关重要。深入研究这些联系,可以让我们更深入地了解我们的免疫系统在愈合中的作用,以及更好地理解肠道炎症性疾病。