Roles of the ACE/Ang II/AT1R pathway, cytokine release, and alteration of tight junctions in COVID-19 pathogenesis.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Tissue Barriers Pub Date : 2023-04-03 DOI:10.1080/21688370.2022.2090792

Laith Ashour

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引用次数: 5

Abstract

This paper shows how SARS-CoV-2 alters tight junctions (TJs) in human organs. The effect of SARS-CoV-2 on the ACE/Ang II/AT1R pathway and immune cells culminates in the release of numerous pro-inflammatory mediators, leading to the presence of certain symptoms in COVID-19, such as acute lung injury (ALI), pulmonary hypertension, and pulmonary fibrosis. Furthermore, the cytokines released alter different TJs components. The study shows how the irregular release of pro-inflammatory cytokines leads to claudin disruption in various tissues of the body, resulting in different symptoms, such as alveolar fibrosis, pulmonary edema, conjunctivitis, altered fertility in males, gastrointestinal symptoms, Covid toes, and others. SARS-CoV-2 also alters occludin expression in the endothelial and blood-testis barriers (BTB) resulting in edema and altered fertility. Viral disruption of JAM-A leads to activation of the RhoA GTPase, which leads to ALI. Taken together, these results define ACE/Ang II/AT1R pathway receptors and tight junctional components as potential therapeutic targets in COVID-19.

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ACE/Ang II/AT1R通路、细胞因子释放和紧密连接改变在COVID-19发病机制中的作用

本文展示了SARS-CoV-2如何改变人体器官的紧密连接(TJs)。SARS-CoV-2对ACE/Ang II/AT1R通路和免疫细胞的影响最终导致大量促炎介质的释放，导致COVID-19出现某些症状，如急性肺损伤(ALI)、肺动脉高压和肺纤维化。此外，释放的细胞因子改变了不同的TJs成分。该研究表明，促炎细胞因子的不规则释放如何导致身体各组织中的claudin中断，从而导致不同的症状，如肺泡纤维化、肺水肿、结膜炎、男性生育能力改变、胃肠道症状、新冠肺炎等。SARS-CoV-2还会改变内皮和血睾丸屏障(BTB)中的occludin表达，导致水肿和生育能力改变。病毒破坏JAM-A导致RhoA GTPase的激活，从而导致ALI。综上所述，这些结果确定了ACE/Ang II/AT1R通路受体和紧密连接成分是COVID-19的潜在治疗靶点。

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.