Zheng Hanxue, Yang Zhi, Xin Zhenlong, Yang Yang, Yu Yuan, Cui Jihong, Liu Hongbo, Chen Fulin
Lab of Tissue Engineering, Faculty of Life Sciences, Northwest University, 229 TaiBai North Road, Xi'an 710069, China.
Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi'an 710069, China.
Theranostics. 2020 Sep 23;10(25):11737-11753. doi: 10.7150/thno.47717. eCollection 2020.
Fibrosis exists in almost all organs/tissues of the human body, plays an important role in the occurrence and development of diseases and is also a hallmark of the aging process. However, there is no effective prevention or therapeutic method for fibrogenesis. As a serine/threonine (Ser/Thr)-protein kinase, glycogen synthase kinase-3β (GSK-3β) is a vital signaling mediator that participates in a variety of biological events and can inhibit extracellular matrix (ECM) accumulation and the epithelial-mesenchymal transition (EMT) process, thereby exerting its protective role against the fibrosis of various organs/tissues, including the heart, lung, liver, and kidney. Moreover, we further present the upstream regulators and downstream effectors of the GSK-3β pathway during fibrosis and comprehensively summarize the roles of GSK-3β in the regulation of fibrosis and provide several potential targets for research. Collectively, the information reviewed here highlights recent advances vital for experimental research and clinical development, illuminating the possibility of GSK-3β as a novel therapeutic target for the management of tissue fibrosis in the future.
纤维化存在于人体几乎所有器官/组织中，在疾病的发生和发展中起重要作用，也是衰老过程的一个标志。然而，目前尚无有效的预防或治疗纤维化形成的方法。糖原合酶激酶-3β（GSK-3β）作为一种丝氨酸/苏氨酸（Ser/Thr）蛋白激酶，是一种重要的信号转导介质，参与多种生物学事件，能够抑制细胞外基质（ECM）积累和上皮-间质转化（EMT）过程，从而对包括心脏、肺、肝脏和肾脏在内的各种器官/组织的纤维化发挥保护作用。此外，我们进一步介绍了纤维化过程中GSK-3β信号通路的上游调节因子和下游效应器，并全面总结了GSK-3β在纤维化调节中的作用，提供了几个潜在的研究靶点。总的来说，本文综述的信息突出了对实验研究和临床开发至关重要的最新进展，阐明了GSK-3β作为未来组织纤维化管理新治疗靶点的可能性。
