Faculty of Life Science & Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
Faculty of Life Science & Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
Ageing Res Rev. 2022 Aug;79:101662. doi: 10.1016/j.arr.2022.101662. Epub 2022 Jun 7.
Aging promotes chronic inflammation, which contributes to fibrosis and decreases organ function. Fibrosis, the excessive synthesis and deposition of extracellular matrix components, is the main cause of most chronic diseases including aging-related organ failure. Organ fibrosis in the heart, liver, and kidneys is the final manifestation of many chronic diseases. The aryl hydrocarbon receptor (AHR) is a cytoplasmic receptor and highly conserved transcription factor that is activated by a variety of small-molecule ligands to affect a wide array of tissue homeostasis functions. In recent years, mounting evidence has revealed that AHR plays an important role in multi-organ fibrosis initiation, progression, and therapy. In this review, we summarise the relationship between AHR and the pathogenesis of aging-related tissue fibrosis, and further discuss how AHR modulates tissue fibrosis by regulating transforming growth factor-β signalling, immune response, and mitochondrial function, which may offer novel targets for the prevention and treatment of this condition.
衰老是促进慢性炎症的主要原因，慢性炎症可导致纤维化并降低器官功能。纤维化是大多数慢性疾病（包括与年龄相关的器官衰竭）的主要原因，其是细胞外基质成分过度合成和沉积的结果。心脏、肝脏和肾脏的器官纤维化是许多慢性疾病的终末表现。芳香烃受体 (AHR) 是一种细胞质受体和高度保守的转录因子，可被多种小分子配体激活，从而影响广泛的组织稳态功能。近年来，越来越多的证据表明 AHR 在多器官纤维化的发生、进展和治疗中发挥着重要作用。在这篇综述中，我们总结了 AHR 与与年龄相关的组织纤维化发病机制之间的关系，并进一步讨论了 AHR 如何通过调节转化生长因子-β信号、免疫反应和线粒体功能来调节组织纤维化，这可能为预防和治疗这种疾病提供新的靶点。
