Wang Si-Jia, Yuan Fuwen, Yin Lei-Miao
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
J Transl Med. 2025 Sep 2;23(1):978. doi: 10.1186/s12967-025-06997-z.
PIP5K1α is a key member of the lipid kinase family, involved in several cellular processes including cell proliferation and differentiation, cytoskeletal remodeling, inositol-phospholipid signaling, intracellular vesicle transport, and protein secretion. Emerging evidence now highlights critical functions of PIP5K1α in asthma-related biological processes. In this review, we aim to consolidate existing literature on the involvement of PIP5K1α in asthma pathogenesis. We summarize PIP5K1α-related pathways that regulate airway immune homeostasis (regulating T cell/ILCs-mediated immune response, TLR4/MyD88/NF-κB signaling pathway, Let-7 miRNA biogenesis, and its regulatory modifications), airway hyper-responsiveness (modulating of calcium release, airway smooth muscle contractility, and epithelial barrier dysfunction), and airway remodeling (regulating cell migration, proliferation, epithelial remodeling, and cytoskeleton modulation) in asthma. Although clinically approved PIP5K1α inhibitors are currently unavailable, targeting this kinase present a compelling therapeutic strategy for asthma, requiring further research into develop effective treatments.
磷脂酰肌醇-4-磷酸5-激酶1α（PIP5K1α）是脂质激酶家族的关键成员，参与多种细胞过程，包括细胞增殖与分化、细胞骨架重塑、肌醇磷脂信号传导、细胞内囊泡运输和蛋白质分泌。新出现的证据凸显了PIP5K1α在哮喘相关生物学过程中的关键作用。在本综述中，我们旨在整合现有关于PIP5K1α参与哮喘发病机制的文献。我们总结了PIP5K1α相关途径，这些途径调节哮喘中的气道免疫稳态（调节T细胞/固有淋巴细胞介导的免疫反应、Toll样受体4/髓样分化因子88/核因子κB信号通路、Let-7微小RNA生物合成及其调控修饰）、气道高反应性（调节钙释放、气道平滑肌收缩性和上皮屏障功能障碍）以及气道重塑（调节细胞迁移、增殖、上皮重塑和细胞骨架调节）。尽管目前尚无临床批准的PIP5K1α抑制剂，但靶向该激酶为哮喘提供了一种有吸引力的治疗策略，需要进一步研究以开发有效的治疗方法。
