Macrophage-to-myofibroblast transition promotes pulmonary fibrosis occurred in LPS-induced acute lung injury of mouse models
10.16352/j.issn.1001-6325.2024.03.0281
- VernacularTitle:巨噬细胞向肌成纤维细胞转化促进LPS诱导的急性肺损伤模型小鼠肺纤维化
- Author:
Dong ZHAO
1
;
Shiqian ZHA
;
Yixuan WANG
;
Zhou PAN
;
Wenzhen YU
;
Ke HU
Author Information
1. 武汉大学人民医院 呼吸与危重症医学科二科,湖北 武汉 430060
- Keywords:
macrophage-to-myofibroblast transition;
lung injury;
pulmonary fibrosis
- From:
Basic & Clinical Medicine
2024;44(3):281-287
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P＜0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P＜0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P＜0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P＜0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P＜0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.
