Yu Hang-Xing, Feng Zhe, Lin Wei, Yang Kang, Liu Rui-Qi, Li Jia-Qi, Liu Xin-Yue, Pei Ming, Yang Hong-Tao
1Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Aging Dis. 2022 Jun 1;13(3):732-752. doi: 10.14336/AD.2021.1105. eCollection 2022 Jun.
Fibrosis is a pathological manifestation of wound healing that replaces dead/damaged tissue with collagen-rich scar tissue to maintain homeostasis, and complications from fibrosis contribute to nearly half of all deaths in the industrialized world. Ageing is closely associated with a progressive decline in organ function, and the prevalence of tissue fibrosis dramatically increases with age. Despite the heavy clinical and economic burden of organ fibrosis as the population ages, to date, there is a paucity of therapeutic strategies that are specifically designed to slow fibrosis. Aryl hydrocarbon receptor (AhR) is an environment-sensing transcription factor that exacerbates aging phenotypes in different tissues that has been brought back into the spotlight again with economic development since AhR could interact with persistent organic pollutants derived from incomplete waste combustion. In addition, gut microbiota dysbiosis plays a pivotal role in the pathogenesis of numerous diseases, and microbiota-associated tryptophan metabolites are dedicated contributors to fibrogenesis by acting as AhR ligands. Therefore, a better understanding of the effects of tryptophan metabolites on fibrosis modulation through AhR may facilitate the exploitation of new therapeutic avenues for patients with organ fibrosis. In this review, we primarily focus on how tryptophan-derived metabolites are involved in renal fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis and cardiac fibrosis. Moreover, a series of ongoing clinical trials are highlighted.
纤维化是伤口愈合的一种病理表现，它用富含胶原蛋白的瘢痕组织替代死亡/受损组织以维持体内平衡，并且纤维化引发的并发症导致工业化国家近一半的死亡。衰老与器官功能的逐渐衰退密切相关，组织纤维化的患病率也随年龄增长而显著增加。尽管随着人口老龄化，器官纤维化带来了沉重的临床和经济负担，但迄今为止，专门用于减缓纤维化的治疗策略仍然匮乏。芳烃受体（AhR）是一种环境感应转录因子，它会加剧不同组织中的衰老表型，随着经济发展，AhR再次成为焦点，因为它能与不完全废物燃烧产生的持久性有机污染物相互作用。此外，肠道微生物群失调在多种疾病的发病机制中起关键作用，微生物群相关的色氨酸代谢产物作为AhR配体，是纤维化形成的重要因素。因此，更好地了解色氨酸代谢产物通过AhR对纤维化调节的影响，可能有助于为器官纤维化患者开发新的治疗途径。在这篇综述中，我们主要关注色氨酸衍生的代谢产物如何参与肾纤维化、特发性肺纤维化、肝纤维化和心脏纤维化。此外，还重点介绍了一系列正在进行的临床试验。
