Uddin Md Jamal, Dorotea Debra, Pak Eun Seon, Ha Hunjoo
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea.
Biomol Ther (Seoul). 2020 May 1;28(3):213-221. doi: 10.4062/biomolther.2019.214.
Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a nonreceptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.
急性肾损伤（AKI）是一种常见疾病，其病理生理学复杂，对慢性肾脏病和终末期肾衰竭的发展有显著影响。因此，预防AKI可降低死亡率、发病率和医疗负担。然而，目前尚无有效的药物用于预防或治疗AKI。开发具有多效性、能覆盖多种病理生理途径的治疗药物可能在减轻AKI方面更有效。Fyn是一种非受体酪氨酸激酶，已被认为可整合肾脏中的多种损伤性刺激。有限的研究表明，在实验性AKI中Fyn转录水平和活性增加。激活的Fyn激酶可促进与AKI进展相关的各种下游信号通路，如氧化应激、炎症、内质网应激以及自噬功能障碍。Fyn激酶在介导各种病理生理途径方面的多功能性表明，抑制它可能是减轻AKI的一种潜在策略。
