Lialios Peter, Alimperti Stella
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, United States.
Center for Biological and Biomedical Engineering, Georgetown University, Washington, DC, United States.
Front Cell Infect Microbiol. 2025 Feb 11;15:1506636. doi: 10.3389/fcimb.2025.1506636. eCollection 2025.
Epithelial barriers serve as critical defense lines against microbial infiltration and maintain tissue homeostasis. E-cadherin, an essential component of adherens junctions, has emerged as a pivotal molecule that secures epithelial homeostasis. Lately, its pleiotropic role beyond barrier function, including its involvement in immune responses, has become more evident. Herein, we delve into the intricate relationship between (dys)regulation of epithelial homeostasis and the versatile functionality of E-cadherin, describing complex mechanisms that underlie barrier integrity and disruption in disease pathogenesis such as bacterial infection and inflammation, among others. Clinical implications of E-cadherin perturbations in host pathophysiology are emphasized; downregulation, proteolytic phenomena, abnormal localization/signaling and aberrant immune reactions are linked with a broad spectrum of pathology beyond infectious diseases. Finally, potential therapeutic interventions that may harness E-cadherin to mitigate barrier-associated tissue damage are explored. Overall, this review highlights the crucial role of E-cadherin in systemic health, offering insights that could pave the way for strategies to reinforce/restore barrier integrity and treat related diseases.
上皮屏障是抵御微生物入侵的关键防线,并维持组织稳态。E-钙黏蛋白是黏着连接的重要组成部分,已成为确保上皮稳态的关键分子。最近,其在屏障功能之外的多效性作用,包括参与免疫反应,变得更加明显。在此,我们深入探讨上皮稳态(失调)与E-钙黏蛋白多功能性之间的复杂关系,描述在诸如细菌感染和炎症等疾病发病机制中构成屏障完整性和破坏的复杂机制。强调了E-钙黏蛋白扰动在宿主病理生理学中的临床意义;下调、蛋白水解现象、异常定位/信号传导和异常免疫反应与传染病以外的广泛病理相关。最后,探索了可能利用E-钙黏蛋白减轻屏障相关组织损伤的潜在治疗干预措施。总体而言,本综述强调了E-钙黏蛋白在全身健康中的关键作用,为加强/恢复屏障完整性和治疗相关疾病的策略提供了思路。