Jayne David, Herbert Corentin, Anquetil Vincent, Teixeira Geoffrey
Department of Medicine, University of Cambridge, Cambridge, UK.
Alentis Therapeutics, Allschwil, Switzerland.
Nephron. 2025;149(4):240-250. doi: 10.1159/000542498. Epub 2024 Nov 12.
Kidney disease poses a significant global health challenge, marked by a rapid decline in renal function due to a variety of causative factors. A crucial element in the pathophysiology of kidney disease is the dysregulation of epithelial cells, which are vital components of renal tissue architecture. The integrity and functionality of these cells are largely dependent on tight junctions (TJ) proteins, complex molecular structures that link adjacent epithelial cells. These TJ not only confer cellular polarity and maintain essential barrier functions but also regulate epithelial permeability.
TJ proteins are pivotal in their traditional role at cell junctions and in their non-junctional capacities. Recent research has shifted the perception of these proteins from mere structural elements to dynamic mediators of kidney disease, playing significant roles in various renal pathologies. This review explores the multifaceted roles of TJ proteins, focusing on their functions both within and external to the renal epithelial junctions. It highlights how these proteins contribute to mechanisms underlying kidney disease, emphasizing their impact on disease progression and outcomes.
TJ proteins have emerged as significant players in the field of nephrology, not only for their structural role but also for their regulatory functions in disease pathology. Their dual roles in maintaining epithelial integrity and mediating pathological processes make them promising therapeutic targets for kidney disease. Understanding the intricate contributions of TJ proteins in kidney pathology offers potential for novel therapeutic strategies, aiming to modulate these proteins to halt or reverse the progression of kidney disease.
肾脏疾病是一项重大的全球健康挑战,其特征是由于多种致病因素导致肾功能迅速下降。肾脏疾病病理生理学中的一个关键因素是上皮细胞失调,上皮细胞是肾组织结构的重要组成部分。这些细胞的完整性和功能在很大程度上依赖于紧密连接(TJ)蛋白,紧密连接是连接相邻上皮细胞的复杂分子结构。这些紧密连接不仅赋予细胞极性并维持基本的屏障功能,还调节上皮通透性。
紧密连接蛋白在其传统的细胞连接作用及其非连接功能中都起着关键作用。最近的研究已将对这些蛋白的认识从单纯的结构元件转变为肾脏疾病的动态介质,它们在各种肾脏病理中发挥着重要作用。本综述探讨了紧密连接蛋白的多方面作用,重点关注它们在肾上皮连接内部和外部的功能。它强调了这些蛋白如何促成肾脏疾病的潜在机制,强调了它们对疾病进展和结果的影响。
紧密连接蛋白已成为肾脏病学领域的重要参与者,不仅因其结构作用,还因其在疾病病理学中的调节功能。它们在维持上皮完整性和介导病理过程中的双重作用使其成为肾脏疾病有前景的治疗靶点。了解紧密连接蛋白在肾脏病理中的复杂作用为新型治疗策略提供了潜力,旨在调节这些蛋白以阻止或逆转肾脏疾病的进展。