Background: KLF15 is involved in cardiovascular disease processes by regulating vascular remodeling and metabolic disorders. Macrophages mediate the inflammatory response in deep vein thrombosis (DVT) by secreting inflammatory cytokines and modulating the fibrinolytic system. Therefore, this study aims to discuss the effect of KLF15 on macrophage polarization in DVT. Methods: In vivo, a DVT animal model was used to assess KLF15 expression and macrophage polarization. In vitro, PMA-treated THP-1 cells with KLF15 overexpression were differentiated into M1-and M2-like macrophages, with polarization markers analyzed by molecular and cellular assays. Results: In vivo experiments, levels of KLF15, iNOS, CD206, IL-1(3, IL-6, IL-10 and TGF-(3 were increased in the DVT animal model. In vitro experiments, KLF15 overexpression augmented iNOS, CD86, IL-12, TNF-alpha, IL-1(3, and IL-6 levels in M1-like macrophages. Additionally, KLF15 overexpression diminished CD206, IL-10, ARG1, IL-10 and TGF-(3 levels in M2-like macrophages. In CUT&Tag, peaks bound to KLF15 and lgG were mainly located in the promoter and intronic regions, and KLF15 protein bound more peaks than lgG near the TSS site. YY1, EIF4E, LCK, HMGB1, GPD2, MORF4L1, HIPK2 and NEK2 were hub genes in the peaks that bind to KLF15. ChIP assay confirmed that KLF15 bound the NEK2 promoter in M1-like macrophages and enhanced its transcription and NF kappa B pathway activity. Conclusion: KLF15 facilitates M1 macrophage polarization in DVT via the NEK2/NF-kappa B pathway, highlighting its potential as a therapeutic target for DVT management. Future studies are warranted to explore its clinical applicability and mechanistic nuances.
基金：
Yunnan Fundamental Research Projects [202401AT070180]; Yunnan University of Chinese Medicine Joint Fund Project [XYLH202211]; High-level Talents for Traditional Chinese Medicine Discipline in Yunnan Province [2024103]; National Natural Science Foundation of China [82160101]; Priority Union Foundation of Yunnan Provincial Science and Technology Department and Kunming Medical University [202201AY070001059]; Yunnan Health Training Project of High-Level Talents [H2024084]; Yunnan Revitalization Talent Support Program
第一作者机构：[1]Yunnan Univ Chinese Med, Sch Clin Med 1, 1076 Yuhua Rd, Kunming 650500, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[*1]Kunming Med Univ, Dept Sports Med, Affiliated Hosp 1, 295 Xichang Rd, Kunming 650032, Peoples R China[2]Kunming Med Univ, Dept Sports Med, Affiliated Hosp 1, 295 Xichang Rd, Kunming 650032, Peoples R China
推荐引用方式(GB/T 7714)：
Li Jizheng,Xiang YaoYu,Shentu Haopeng,et al.KLF15 regulates macrophage polarization patterns in deep vein thrombosis[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2025,155:114632.doi:10.1016/j.intimp.2025.114632.
APA：
Li, Jizheng,Xiang, YaoYu,Shentu, Haopeng,Yang, Xianguang,Yang, Jing...&Song, En.(2025).KLF15 regulates macrophage polarization patterns in deep vein thrombosis.INTERNATIONAL IMMUNOPHARMACOLOGY,155,
MLA：
Li, Jizheng,et al."KLF15 regulates macrophage polarization patterns in deep vein thrombosis".INTERNATIONAL IMMUNOPHARMACOLOGY 155.(2025)
