School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana, USA.
Cell Biochem Funct. 2024 Dec;42(8):e70007. doi: 10.1002/cbf.70007.
The endothelial semipermeable monolayers ensure tissue homeostasis, are subjected to a plethora of stimuli, and their function depends on cytoskeletal integrity and remodeling. The permeability of those membranes can fluctuate to maintain organ homeostasis. In cases of severe injury, inflammation or disease, barrier hyperpermeability can cause irreparable damage of endothelium-dependent issues, and eventually death. Elucidation of the signaling regulating cytoskeletal structure and barrier integrity promotes the development of targeted pharmacotherapies towards disorders related to the impaired endothelium (e.g., acute respiratory distress syndrome, sepsis). Recent reports investigate the role of unfolded protein response in barrier function. Herein we review the cytoskeletal components, the unfolded protein response function; and their interrelations on health and disorder. Moreover, we emphasize on unfolded protein response modulators, since they ameliorate illness related to endothelial leak.
内皮细胞半透性单层可确保组织内环境稳定,其会受到大量刺激,其功能取决于细胞骨架的完整性和重塑。这些膜的通透性可以波动以维持器官内环境稳定。在严重损伤、炎症或疾病的情况下,屏障通透性增加可导致内皮细胞依赖性问题的不可逆转损伤,最终导致死亡。阐明调节细胞骨架结构和屏障完整性的信号转导可促进针对与受损内皮相关的疾病(例如,急性呼吸窘迫综合征、败血症)的靶向药物治疗的发展。最近的报告研究了未折叠蛋白反应在屏障功能中的作用。本文综述了细胞骨架成分、未折叠蛋白反应功能及其在健康和疾病中的相互关系。此外,我们还强调了未折叠蛋白反应调节剂,因为它们可改善与内皮细胞渗漏相关的疾病。