Department of Rheumatology and Immunology, Affiliated Hospital of Yangzhou University, Yangzhou 225003, Jiangsu Province, China.
Graduate School of Dalian Medical University, Dalian 116044, Liaoning Province, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Jun 19;53(3):376-381. doi: 10.3724/zdxbyxb-2023-0567.
The core components of the Hippo signaling pathway encompass upstream regulatory molecules, core kinase cascade complexes, and downstream transcriptional regulation complexes. This pathway modulates cellular behaviors by influencing the effector molecules of its core components and plays a pivotal role in immune regulation. Effector molecules,such as Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), transcriptional enhanced associate domain transcriptional factor (TEAD), monopolar spindle-one binder (MOB1), large tumor suppressor (LATS), can stimulate fibroblast-like synovial cell migration and invasion in rheumatoid arthritis, regulate osteoarthritis disease progression, promote pathological new bone formation in ankylosing spondylitis, sustain submandibular gland development while delaying Sjogren's syndrome progression, mediate alpha-smooth muscle actin in systemic sclerosis, and refine the regulation of target genes associated with pulmonary fibrosis. This article provides an overview of the regulatory mechanisms involving Hippo signaling pathway-related effector molecules in the pathogenesis and progression of rheumatic immune system diseases, to serve as a reference for exploring novel therapeutic targets of rheumatic immune system diseases.
Hippo 信号通路的核心组成部分包括上游调节分子、核心激酶级联复合物和下游转录调节复合物。该通路通过影响其核心成分的效应分子来调节细胞行为，在免疫调节中发挥关键作用。效应分子，如 Yes 相关蛋白 (YAP)、含 PDZ 结合基序的转录共激活因子 (TAZ)、转录增强相关域转录因子 (TEAD)、单极纺锤体结合蛋白 1 (MOB1)、大肿瘤抑制因子 (LATS)，可刺激类风湿关节炎中成纤维样滑膜细胞的迁移和侵袭，调节骨关节炎疾病进展，促进强直性脊柱炎病理性新骨形成，维持下颌下腺发育同时延缓干燥综合征进展，介导系统性硬化症中的α-平滑肌肌动蛋白，并精细调控与肺纤维化相关的靶基因。本文概述了 Hippo 信号通路相关效应分子在风湿免疫性疾病发病和进展中的调控机制，为探索风湿免疫性疾病的新型治疗靶点提供参考。
