医学分子生物学杂志2025，Vol.22Issue(2)：146-152,172,8.DOI:10.3870/j.issn.1672-8009.2025.02.007
常山酮通过巨噬细胞介导的子宫内膜基质细胞生物学行为参与调控子宫内膜异位症的作用研究
Effect of Halofuginone on Proliferation and Apoptosis of Endometrial Stromal Cells through Macrophage-Mediated Pathways in the Patho-genesis of Endometriosis
摘要
Abstract
Objective To investigate the effect of halofuginone(HF)on proliferation and ap-optosis of endometriotic stromal cells(ESCs)in endometriosis(EMs)by regulation of macro-phage polarization through peroxisome proliferator-activated receptor gamma(PPARG)-leukemia inhibitory factor(LIF)axis.Methods Normal endometrial stromal cells(NESCs)and ectopic endometrial stromal cells(EESCs)were treated with different concentrations of HF.CCK8 assay was used to detect the cell proliferation activity,and TUNEL assay was used to detect the cell apop-tosis.Bioinformatics analysis was performed to identify the intersection of targets of HF,EMs,and macrophage.A co-culture system of macrophages and EESCs was established,cells were then divid-ed into 7 groups:M0+EESCs group、M2+EESCs group、M2+EESCsHF group、M0+EESC-soe-PPARG group、M0+EESCssh-PPARG group、M0+EESCsoe-PPARG+oe-LIF group、M0+EESCsoe-PPARG+HF group.ELISA was used to detect the concentrations of M1 macrophage markers(iNOS,IL-6)and M2 macrophage markers(Arg-1,TGF-β)in the cell supernatant.CCK8 and TUNEL assay were used to detect the proliferation and apoptosis of EESCs,respectively.Results HF had no signifi-cant effect on the proliferation activity of NESCs(F=0.195,P=0.959),but significantly inhib-ited the proliferation of EESCs and promoted cell apoptosis(P<0.05).The levels of iNOS and IL-6 in the M2+EESCs group were decreased when compared with those in the M0+EESCs group,while the levels of Arg-1 and TGF-β were increased.In addition,the proliferation activity of EESCs was increased and the apoptosis was decreased.HF intervention reversed the results above(P<0.05).PPARG was identified as a key target in this study through bioinformatics analysis and litera-ture search.The levels of iNOS and IL-6 in the cell supernatant of the M0+EESCsoe-PPARG group were decreased,while the levels of Arg-1 and TGF-β were increased when compared with those in the M0+EESCs group.The proliferation activity of EESCs were increased and apoptosis were decreased(P<0.05),while an opposite results were obtained in the M0+EESCssh-PPARG group(P<0.05).Furthermore,upregulation of LIF expression or HF intervention in the M0+EESCsoe-PPARG+oe-LIF and M0+EESCsoe-PPARG+HF groups led to the increase of iNOS and IL-6 levels and proliferation activity of EESCs,and the decrease of Arg-1 and TGF-β and apoptosis when compared with the M0+EESC-soe-PPARG group(P<0.05).Conclusion HF inhibits M2 polarization of macrophages and inhibits the proliferation of EESCs while promoting cell apoptosis by regulating the PPARG-LIF signaling pathway.关键词
常山酮/过氧化物酶体增殖物激活受体γ/白血病抑制因子/巨噬细胞/子宫内膜异位症/子宫内膜异位基质细胞Key words
halofuginone/peroxisome proliferator-activated receptor gamma/leukemia inhibi-tory factor/macrophages/endometriosis/endometrial stromal cells分类
临床医学引用本文复制引用
曹文超..常山酮通过巨噬细胞介导的子宫内膜基质细胞生物学行为参与调控子宫内膜异位症的作用研究[J].医学分子生物学杂志,2025,22(2):146-152,172,8.基金项目
首都临床诊疗技术研究及转换应用(省级)(No.Z2011000552085) This work was supported by a grand from the Research and Application of Clinical Diagnosis and Treatment Technology in the Capital City(No.Z2011000552085) （省级）
