Claudins as signaling hubs of fibrosis, autophagy, and metabolism.

IF 3.1 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Tissue Barriers Pub Date : 2026-07-16 DOI:10.1080/21688370.2026.2703918

Haruna Fukunaga, Yuki Niwa, Masuo Kondoh

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引用次数: 0

Abstract

Claudins were identified in 1998 as structural and functional components of tight junction (TJ) seals between adjacent epithelial cells. Since their identification, pharmaceutical research has mainly focused on junctional claudins. For example, permeation enhancers that modulate claudin-based TJ seals have been developed to enhance gastrointestinal, pulmonary, and epidermal absorption of drugs. Inflammation, a common feature of various diseases, is often accompanied by the disruption of claudin-based seals. Consequently, junctional claudin modulators have been developed for treating inflammatory diseases. In 2022, antibodies against non-junctional claudin-1 were produced, and these antibodies attenuated hepatic fibrosis by inhibiting a fibrotic signaling pathway that depends on non-junctional claudin-1. Claudin-targeted drug development has entered a new era, transitioning from the barrier function of TJ claudins to signaling hub-associated claudins. In this review, we discuss recent findings on claudins as drug targets in relation to fibrosis, autophagy, and metabolism, focusing specifically on their functions as signaling hubs.

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Claudins作为纤维化、自噬和代谢的信号中枢。

cladin于1998年被确定为邻近上皮细胞之间紧密连接（TJ）密封的结构和功能成分。自它们被发现以来，药物研究主要集中在连接蛋白上。例如，已经开发出调节基于claudin的TJ封印的渗透增强剂，以增强胃肠道、肺部和表皮对药物的吸收。炎症是各种疾病的共同特征，通常伴随着基于claudn的海豹的破坏。因此，结缔组织蛋白调节剂已被开发用于治疗炎症性疾病。在2022年，抗非连接claudin-1的抗体被生产出来，这些抗体通过抑制依赖于非连接claudin-1的纤维化信号通路来减轻肝纤维化。claudin靶向药物的开发已经进入了一个新的时代，从TJ claudin的屏障功能过渡到信号中枢相关claudin。在这篇综述中，我们讨论了最近关于claudin作为纤维化、自噬和代谢相关药物靶点的发现，特别关注它们作为信号中枢的功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.60

自引率

6.50%

发文量

期刊介绍： Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.