Department of Clinical Biochemistry and.
Autophagy Research Center, Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
Am J Respir Cell Mol Biol. 2021 Jan;64(1):29-38. doi: 10.1165/rcmb.2019-0235TR.
Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER), resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs. Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions, such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Furthermore, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Furthermore, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage. We also present an overview of the pathogenic mechanisms, with a brief focus on potential strategies for pharmacological interventions.
肺细胞不断受到各种内外应激源的影响，这些应激源会破坏蛋白质的内环境稳态。为了应对这些刺激，细胞会引发一种高度保守的适应性机制，称为未折叠蛋白反应（UPR）。UPR 应激源会对内质网（ER）施加更大的蛋白质分泌需求，从而使这些细胞类型得以发展、分化和存活，以满足这些不断增加的功能需求。UPR 的失调会导致疾病的发生。UPR 和 ER 应激与几种人类疾病有关，如慢性炎症、神经退行性疾病、代谢综合征和癌症。此外，针对 UPR 途径的有效且特异的化合物正在被开发为未来的治疗方法。本综述的重点是全面描述内、外应激源对哮喘中 ER 的影响。此外，我们还讨论了 UPR 信号通路如何在肺部被激活以克服细胞损伤。我们还概述了发病机制，并简要介绍了潜在的药理学干预策略。
