Unfolded protein response modulates the effects of GHRH antagonists in experimental models of in vivo and in vitro lung injury.

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

Abstract

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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