Evolocumab protects mice from radiation-induced damage by affecting hematopoietic cell lineage

作者：Yuhan Gan, Jiawei Zhou, Bendong Li, Daqian Huang, Yuejun Ma, Lu Pei, Kaiwen Sheng, Liao Zhang, Ying Cheng, Jicong Du, Shengyun Cai, Cong Liu · 发表于：Genomics · 年份：2026 · DOI：10.1016/j.ygeno.2026.111277 · 研究领域：Effects of Radiation Exposure、Cancer-related Molecular Pathways、Carcinogens and Genotoxicity Assessment

Background The hematopoietic system is extremely sensitive to ionizing radiation(IR) and is easily damaged after exposure. Recent studies [1, 2] have shown that hematopoietic lineage differentiation may play a key role in Ionizing radiation -induced acute injury. Methods C57BL/6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Evolocumab (80.0 mg/kg) or MMP9-IN (20.0 mg/kg). Survival time, body weight, pathology, hematopoietic cell differentiation changes and organoids of the mice after IR (10.0 Gy) were compared, and the mechanism of action in tissues was verified by transcriptome sequencing. Results Ionizing radiation can inhibit hematopoietic cell lineage differentiation and affect cholesterol metabolism. The expression of the Pcsk9 gene was significantly upregulated after IR. Treatment with a Pcsk9 monoclonal antibody (Evolocumab) exerted significant radioprotective effects, including improving the survival rate of irradiated mice, reducing body weight loss, preserving the integrity of the bone marrow cavity, and promoting cellular proliferation. Flow cytometric analysis showed that Evolocumab significantly increased hematopoietic precursor cells and hematopoietic stem cells and promoted their differentiation into ST-LSKs and MPPs. In addition, the proportions of CMPs and GMPs were increased, whereas the proportion of MEPs was decreased. RNA sequencing results suggested that the IR-induced downregulation of Cd3e within the ...