Wang Yan, Del Borgo Mark, Lee Huey W, Baraldi Dhaniel, Hirmiz Baydaa, Gaspari Tracey A, Denton Kate M, Aguilar Marie-Isabel, Samuel Chrishan S, Widdop Robert E
Department of Pharmacology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, ClaytonVIC, Australia.
Department of Biochemistry and Molecular Biology, Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, ClaytonVIC, Australia.
Front Pharmacol. 2017 Aug 31;8:564. doi: 10.3389/fphar.2017.00564. eCollection 2017.
There are a number of therapeutic targets to treat organ fibrosis that are under investigation in preclinical models. There is increasing evidence that stimulation of the angiotensin II type 2 receptor (ATR) is a novel anti-fibrotic strategy and we have reviewed the published preclinical data relating to the effects of compound 21 (C21), which is the only nonpeptide ATR agonist that is currently available for use in chronic preclinical studies. In particular, the differential influence of ATR on extracellular matrix status in various preclinical fibrotic models is discussed. Collectively, these studies demonstrate that pharmacological ATR stimulation using C21 decreases organ fibrosis, which has been most studied in the setting of cardiovascular and renal disease. In addition, ATR-mediated anti-inflammatory effects may contribute to the beneficial ATR-mediated anti-fibrotic effects seen in preclinical models.
有许多治疗器官纤维化的治疗靶点正在临床前模型中进行研究。越来越多的证据表明，刺激血管紧张素II 2型受体（ATR）是一种新型抗纤维化策略，我们回顾了已发表的关于化合物21（C21）作用的临床前数据，C21是目前唯一可用于慢性临床前研究的非肽类ATR激动剂。特别讨论了ATR在各种临床前纤维化模型中对细胞外基质状态的不同影响。总体而言，这些研究表明，使用C21进行药理学ATR刺激可减少器官纤维化，这在心血管和肾脏疾病的背景下研究最多。此外，ATR介导的抗炎作用可能有助于在临床前模型中观察到的有益的ATR介导的抗纤维化作用。
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