Jridi Imen, Canté-Barrett Kirsten, Pike-Overzet Karin, Staal Frank J T
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.
Front Cell Dev Biol. 2021 Feb 4;8:615131. doi: 10.3389/fcell.2020.615131. eCollection 2020.
Wnt proteins comprise a large family of highly conserved glycoproteins known for their role in development, cell fate specification, tissue regeneration, and tissue homeostasis. Aberrant Wnt signaling is linked to developmental defects, malignant transformation, and carcinogenesis as well as to inflammation. Mounting evidence from recent research suggests that a dysregulated activation of Wnt signaling is involved in the pathogenesis of chronic inflammatory diseases, such as neuroinflammation, cancer-mediated inflammation, and metabolic inflammatory diseases. Recent findings highlight the role of Wnt in the modulation of inflammatory cytokine production, such as NF-kB signaling and in innate defense mechanisms as well as in the bridging of innate and adaptive immunity. This sparked the development of novel therapeutic treatments against inflammatory diseases based on Wnt modulation. Here, we summarize the role and function of the Wnt pathway in inflammatory diseases and focus on Wnt signaling as underlying master regulator of inflammation that can be therapeutically targeted.
Wnt蛋白构成了一个高度保守的糖蛋白大家族,以其在发育、细胞命运决定、组织再生和组织稳态中的作用而闻名。异常的Wnt信号传导与发育缺陷、恶性转化、致癌作用以及炎症相关。最近研究的越来越多的证据表明,Wnt信号传导的失调激活参与了慢性炎症性疾病的发病机制,如神经炎症、癌症介导的炎症和代谢性炎症性疾病。最近的发现突出了Wnt在调节炎性细胞因子产生中的作用,如核因子-κB信号传导以及在固有防御机制中,以及在固有免疫和适应性免疫的衔接中。这引发了基于Wnt调节的针对炎症性疾病的新型治疗方法的开发。在这里,我们总结了Wnt通路在炎症性疾病中的作用和功能,并聚焦于作为炎症潜在主要调节因子的Wnt信号传导,它可以成为治疗靶点。