Curran Colleen S, Kopp Jeffrey B
Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
Kidney Disease Section, NIDDK, NIH, Bethesda, MD, United States.
Front Pharmacol. 2022 Feb 14;13:782199. doi: 10.3389/fphar.2022.782199. eCollection 2022.
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor that binds diverse endogenous and xenobiotic ligands, which regulate AHR stability, transcriptional activity, and cell signaling. AHR activity is strongly implicated throughout the course of chronic kidney disease (CKD). Many diverse organic molecules bind and activate AHR and these ligands are reported to either promote glomerular and tubular damage or protect against kidney injury. AHR crosstalk with estrogen, peroxisome proliferator-activated receptor-γ, and NF-κB pathways may contribute to the diversity of AHR responses during the various forms and stages of CKD. The roles of AHR in kidney fibrosis, metabolism and the renin angiotensin system are described to offer insight into CKD pathogenesis and therapies.
芳烃受体(AHR)是一种碱性螺旋-环-螺旋转录因子,可结合多种内源性和外源性配体,这些配体调节AHR的稳定性、转录活性和细胞信号传导。在慢性肾脏病(CKD)的整个病程中,AHR活性都有密切关联。许多不同的有机分子可结合并激活AHR,据报道这些配体要么促进肾小球和肾小管损伤,要么预防肾损伤。AHR与雌激素、过氧化物酶体增殖物激活受体-γ和NF-κB信号通路的相互作用,可能导致在CKD的各种形式和阶段中AHR反应的多样性。本文描述了AHR在肾纤维化、代谢和肾素血管紧张素系统中的作用,以期深入了解CKD的发病机制和治疗方法。