Cao Stewart Siyan, Luo Katherine L, Shi Lynn
Columbia University College of Physicians and Surgeons, New York, New York.
J Cell Physiol. 2016 Feb;231(2):288-94. doi: 10.1002/jcp.25098.
The endoplasmic reticulum (ER) is a critical organelle for normal cell function and homeostasis. Disturbance in the protein folding process in the ER, termed ER stress, leads to the activation of unfolded protein response (UPR) that encompasses a complex network of intracellular signaling pathways. The UPR can either restore ER homeostasis or activate pro-apoptotic pathways depending on the type of insults, intensity and duration of the stress, and cell types. ER stress and the UPR have recently been linked to inflammation in a variety of human pathologies including autoimmune, infectious, neurodegenerative, and metabolic disorders. In the cell, ER stress and inflammatory signaling share extensive regulators and effectors in a broad spectrum of biological processes. In spite of different etiologies, the two signaling pathways have been shown to form a vicious cycle in exacerbating cellular dysfunction and causing apoptosis in many cells and tissues. However, the interaction between ER stress and inflammation in many of these diseases remains poorly understood. Further understanding of the biochemistry, cell biology, and physiology may enable the development of novel therapies that spontaneously target these pathogenic pathways.
内质网（ER）是正常细胞功能和体内平衡的关键细胞器。内质网中蛋白质折叠过程的紊乱，即内质网应激，会导致未折叠蛋白反应（UPR）的激活，该反应包含一个复杂的细胞内信号通路网络。根据损伤类型、应激的强度和持续时间以及细胞类型，未折叠蛋白反应可以恢复内质网的稳态，也可以激活促凋亡途径。内质网应激和未折叠蛋白反应最近在包括自身免疫性、感染性、神经退行性和代谢性疾病在内的多种人类病理中与炎症相关联。在细胞中，内质网应激和炎症信号在广泛的生物学过程中共享大量的调节因子和效应器。尽管病因不同，但这两种信号通路在许多细胞和组织中已被证明在加剧细胞功能障碍和导致细胞凋亡方面形成恶性循环。然而，在许多这些疾病中，内质网应激与炎症之间的相互作用仍知之甚少。对生物化学、细胞生物学和生理学的进一步了解可能有助于开发能够自发靶向这些致病途径的新疗法。
