Early diagnostic value and related mechanism of Lnc-IL7R/Jmjd3/KGF axis in inflammatory injury of acute respiratory distress syndrome
10.3969/j.issn.1000-484X.2025.11.005
- VernacularTitle:Lnc-IL7R/Jmjd3/KGF轴对急性呼吸窘迫综合征炎症损伤的早期诊断价值及相关机制
- Author:
Feng ZHOU
1
;
Qixiang YIN
;
Faxing WEI
;
Min WU
;
Haimin LIN
;
Huazhong CAI
Author Information
1. 江苏大学附属医院急诊科,镇江 212001
- Publication Type:Journal Article
- Keywords:
Lnc-IL7R/Jmjd3/KGF axis;
Acute respiratory distress syndrome;
Inflammatory injury
- From:
Chinese Journal of Immunology
2025;41(11):2583-2590
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the early diagnostic value and related mechanism of Lnc-IL7R/Jumonji domain-containing protein 3(Jmjd3)/keratinocyte growth factor(KGF)axis in inflammatory injury of acute respiratory distress syndrome(ARDS).Methods:① RT-qPCR and Western blot were used to detect Lnc-IL7R,Jmjd3,KGF mRNA and protein levels,as well as trimethyl-ation of histone H3 at lysine 27(H3K27)me3 protein level in serum of ARDS patients;ELISA was used to detect IL-1β,IL-6,TNF-α levels in serum.② Mitochondrial damage-associated molecular patterns(MTDs)was used to stimulate HBE cells and create traumatic ARDS cell model.HBE cells were divided into control group,model group(MTDs group),overexpression Lnc-IL7R group(Lnc-IL7R group),overexpression control group(NC group),overexpression Lnc-IL7R+overexpression Jmjd3 group(Lnc-IL7R+Jm-jd3 group).Chromatin immunoprecipitation(ChIP)was used to detect Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in pro-moter region;qRT-PCR and Western blot were used to detect Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,as well as H3K27me3 protein level.③ Injection of MTDs into tail vein of mice was used to create traumatic ARDS mice model.Eighty mice were divided into control group,MTDs group,Lnc-IL7R group,NC group and Lnc-IL7R+Jmjd3 group,with sixteen mice in each group.HE staining was used to detect pathological damage in lung tissue;ChIP and RT-qPCR were used to detect Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region and mRNA levels;ELISA was used to detect IL-1β,IL-6,TNF-α protein levels in BALF;Western blot was used to detect Jmjd3,KGF,H3K27me3 protein levels in lung tissue;immunohisto-chemical staining was used to detect surfactant protein C(SPC)and surfactant protein D(SPD)protein levels in lung tissue.Results:①Compared with healthy individuals,Lnc-IL7R,Jmjd3,KGF mRNA and protein levels,IL-1β,IL-6,TNF-α protein levels in serum of ARDS patients were significant increased,while H3K27me3 protein level was significant decreased(P<0.05).②Compared with control group,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,H3K27me3 protein level in HBE of MTDs group were significant decreased,while Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,Lnc-IL7R were significant increased(P<0.05);after overexpression of Lnc-IL7R,Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,KGF mRNA and protein levels,H3K27me3 protein level were significant increased,Jmjd3,IL-1β,IL-6,TNF-α mRNA and protein levels in lung tissue and BALF were significant decreased(P<0.05);overexpression of Jmjd3 could partially reverse the effects of overexpression of Lnc-IL7R on the above indicators(P<0.05).③Compared with Control group,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,H3K27me3 protein level in lung tissue of MTDs group were significant decreased,while Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,H3K27me3,SPC,SPD protein levels in lung tissue and BALF were significant increased(P<0.05);after overexpression of Lnc-IL7R,Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,KGF mRNA and protein levels,H3K27me3,SPC,SPD protein levels in lung tissue were significant increased,while Jmjd3,IL-1β,IL-6,TNF-α mRNA and protein levels in lung tissue and BALF were significant decreased(P<0.05);overexpression of Jmjd3 could partially reverse the effects of overexpression of Lnc-IL7R on the above indicators(P<0.05).Conclusion:Lnc-IL7R/Jmjd3/KGF axis participates in inflammation regulation and alveolar epithelial cell injury repair in ARDS by regulating histone methylation modifications in the promoter region.Lnc-IL7R/Jmjd3/KGF can be used for early diagnosis of ARDS.
