未折叠蛋白反应调节GHRH拮抗剂在体内和体外肺损伤实验模型中的作用。

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Saikat Fakir, Khadeja-Tul Kubra, Mohammad Shohel Akhter, Mohammad Afaz Uddin, Md Matiur Rahman Sarker, Agnieszka Siejka, Nektarios Barabutis
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引用次数: 0

摘要

开发有效的靶向疗法以改善内皮疾病是当务之急,这一点从最近大流行的破坏性后果中可见一斑。最近的研究表明,未折叠蛋白反应(UPR)调节屏障功能。在目前的研究中,我们揭示了上述高度保守的机制参与了生长激素释放激素拮抗剂(GHRHAnt)在体内和体外对肺损伤的保护作用。在牛肺动脉内皮细胞中,UPR抑制抵消了GHRHAnt对脂多糖(LPS)诱导的内皮细胞高通透性的保护作用。在小鼠肺中,UPR激活增强了GHRHAnt对lps诱导的急性肺损伤的有益作用。我们的观察-主要集中在肺内皮细胞和组织-增强了我们对介导屏障功能机制的认识,并有助于开发针对败血症,直接和间接肺损伤的新疗法。UPR调节对GHRHAnt在其他组织中的作用的影响尚不清楚,这是未来研究的主题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unfolded protein response modulates the effects of GHRH antagonists in experimental models of in vivo and in vitro lung injury.

The development of efficient targeted therapies to ameliorate endothelial disorders is of the utmost need, as evident by the devastating outcomes of the recent pandemic. Recent findings suggest that unfolded protein response (UPR) modulates barrier function. In the current study, we reveal that the aforementioned highly conservative mechanism is involved in the protective effects of growth hormone-releasing hormone antagonists (GHRHAnt) in lung injury, both in vivo and in vitro. In bovine pulmonary artery endothelial cells, UPR suppression counteracted the protective effects of GHRHAnt in lipopolysaccharide (LPS)-induced endothelial hyperpermeability. In mouse lungs, UPR activation enhanced the beneficial effects of GHRHAnt against LPS-induced acute lung injury. Our observations - which are focused on lung endothelial cells and tissues - enhance our knowledge on the mechanisms mediating the barrier function and contribute to the development of novel therapies toward sepsis, direct and indirect lung injury. The effects of UPR modulation on the effects of GHRHAnt in other tissues are unknown, and they are the subject of future investigations.

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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
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.
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