ROBO3 deficiency promotes chemotherapy-induced transition of macrophage to foam cell
10.3969/j.issn.1006-5725.2024.06.010
- VernacularTitle:轴突导向因子受体3缺陷促进化疗药物诱导的巨噬细胞泡沫化进程
- Author:
Yong LIU
1
;
XiaoLei CHENG
;
Xiangli CUI
;
Hao TANG
;
Huanzhen CHEN
Author Information
1. 山西医科大学基础医学院生理学系(太原 030012)
- Keywords:
chemotherapy vascular toxicity;
macrophages-foam cells;
ROBO3;
cholesterol metabo-lism
- From:
The Journal of Practical Medicine
2024;40(6):787-795
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.
