Wang Jincheng, Hu Kaili, Cai Xuanyan, Yang Bo, He Qiaojun, Wang Jiajia, Weng Qinjie
Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Acta Pharm Sin B. 2022 Jan;12(1):18-32. doi: 10.1016/j.apsb.2021.07.023. Epub 2021 Jul 29.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.
特发性肺纤维化（IPF）是一种病因不明的慢性进行性纤维化间质性肺炎。其发病率逐年上升，预后较差，无法治愈。最近，磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（PKB/AKT）信号通路可被视为IPF的主要调节因子。PI3K/AKT在纤维化过程中的作用日益突出，目前PI3K/AKT抑制剂正在IPF的临床评估中。因此，PI3K/AKT代表了纤维化形成过程中的一个关键信号节点，对新型抗纤维化策略的开发具有潜在意义。本综述概括了在理解IPF病因的复杂解读方面所取得的进展，并表明PI3K/AKT能在最大程度上直接参与IPF的形成，或与其他途径协同促进纤维化的发展。我们进一步总结了具有IPF治疗益处的有前景的PI3K/AKT抑制剂，包括临床试验和临床前研究中的抑制剂以及天然产物，并讨论这些抑制剂如何减轻纤维化进展，以探索可能的潜在药物，这将有助于在不久的将来开发出有效的IPF治疗策略。
