Zeng Ruijie, Zhuo Zewei, Luo Yujun, Sha Weihong, Chen Hao
Department of Gastroenterology, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou 510080, China.
Shantou University Medical College, Shantou 515041, China.
iScience. 2021 Dec 14;25(1):103620. doi: 10.1016/j.isci.2021.103620. eCollection 2022 Jan 21.
Rho guanosine triphosphatase (GTPases), as molecular switches, have been identified to be dysregulated and involved in the pathogenesis of various rheumatic diseases, mainly including rheumatoid arthritis, osteoarthritis, systemic sclerosis, and systemic lupus erythematosus. Downstream pathways involving multiple types of cells, such as fibroblasts, chondrocytes, synoviocytes, and immunocytes are mediated by activated Rho GTPases to promote pathogenesis. Targeted therapy via inhibitors of Rho GTPases has been implicated in the treatment of rheumatic diseases, demonstrating promising effects. In this review, the effects of Rho GTPases in the pathogenesis of rheumatic diseases are summarized, and the Rho GTPase-mediated pathways are elucidated. Therapeutic strategies using Rho GTPase inhibitors in rheumatic diseases are also discussed to provide insights for further exploration of targeted therapy in preclinical studies and clinical practice. Future directions on studies of Rho GTPases in rheumatic diseases based on current understandings are provided.
Rho鸟苷三磷酸酶（GTP酶）作为分子开关，已被确定存在失调，并参与多种风湿性疾病的发病机制，主要包括类风湿关节炎、骨关节炎、系统性硬化症和系统性红斑狼疮。涉及多种类型细胞（如成纤维细胞、软骨细胞、滑膜细胞和免疫细胞）的下游信号通路由活化的Rho GTP酶介导，以促进疾病的发生发展。通过Rho GTP酶抑制剂进行的靶向治疗已被应用于风湿性疾病的治疗，并显示出有前景的效果。在本综述中，总结了Rho GTP酶在风湿性疾病发病机制中的作用，并阐明了Rho GTP酶介导的信号通路。还讨论了在风湿性疾病中使用Rho GTP酶抑制剂的治疗策略，为临床前研究和临床实践中进一步探索靶向治疗提供思路。基于目前的认识，给出了风湿性疾病中Rho GTP酶研究的未来方向。
