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Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation.
Cellular and Molecular Life Sciences ( IF 8 ) Pub Date : 2020-09-23 , DOI: 10.1007/s00018-020-03645-1
Jing-Ru Liu 1 , Hua Miao 1 , De-Qiang Deng 2 , Nosratola D Vaziri 3 , Ping Li 4 , Ying-Yong Zhao 1
Affiliation  

The gut microbiota has a crucial effect on regulating the intestinal mucosal immunity and maintaining intestinal homeostasis both in health and in disease state. Many effects are mediated by gut microbiota-derived metabolites and tryptophan, an essential aromatic amino acid, is considered important among many metabolites in the crosstalk between gut microbiota and the host. Kynurenine, serotonin, and indole derivatives are derived from the three major tryptophan metabolism pathways modulated by gut microbiota directly or indirectly. Aryl hydrocarbon receptor (AHR) is a cytoplasmic ligand-activated transcription factor involved in multiple cellular processes. Tryptophan metabolites as ligands can activate AHR signaling in various diseases such as inflammation, oxidative stress injury, cancer, aging-related diseases, cardiovascular diseases (CVD), and chronic kidney diseases (CKD). Accumulated uremic toxins in the body fluids of CKD patients activate AHR and affect disease progression. In this review, we will elucidate the relationship between gut microbiota-derived uremic toxins by tryptophan metabolism and AHR activation in CKD and its complications. This review will provide therapeutic avenues for targeting CKD and concurrently present challenges and opportunities for designing new therapeutic strategies against renal fibrosis.



中文翻译:

肠道菌群衍生的色氨酸代谢通过芳基烃受体信号传导激活介导肾纤维化。

肠道菌群在调节肠道粘膜免疫力和维持肠道健康以及疾病状态方面都具有至关重要的作用。肠道菌群衍生的代谢产物可介导许多作用,而色氨酸(一种必需的芳香族氨基酸)在肠道菌群与宿主之间的串扰中被认为在许多代谢产物中很重要。Kynurenine,5-羟色胺和吲哚衍生物衍生自肠道菌群直接或间接调节的三个主要色氨酸代谢途径。芳烃受体(AHR)是一种涉及多个细胞过程的胞质配体激活转录因子。色氨酸代谢物作为配体可以在各种疾病(例如炎症,氧化应激损伤,癌症,与衰老相关的疾病,心血管疾病(CVD),和慢性肾脏病(CKD)。CKD患者体液中积累的尿毒症毒素会激活AHR并影响疾病进展。在这篇综述中,我们将阐明色氨酸代谢引起的肠道菌群来源的尿毒症毒素与CKD及其并发症的AHR活化之间的关系。这篇综述将为靶向CKD提供治疗途径,同时为设计针对肾纤维化的新治疗策略提出挑战和机遇。

更新日期:2020-09-23
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