Effect of NRIP1 on participating in sepsis-induced intestinal epithelial injury via transcriptional activation of HMGB1
10.3969/j.issn.1000-484X.2025.02.012
- VernacularTitle:NRIP1通过转录激活HMGB1参与脓毒症引起的肠道上皮细胞损伤的作用研究
- Author:
Wenjuan CUI
1
;
Qin LIU
1
;
Xiaoguang FAN
1
;
Lujun QIAO
1
Author Information
1. 胜利油田中心医院重症医学科,东营 257000
- Publication Type:Journal Article
- Keywords:
NRIP1;
HMGB1;
Sepsis;
Intestinal epithelial injury
- From:
Chinese Journal of Immunology
2025;41(2):328-335
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the impacts of nuclear receptor-interacting protein 1(NRIP1)on sepsis-evoked intesti-nal epithelial injury via transcriptional regulation of high mobility group box 1(HMGB1).Methods:The expression levels of NRIP1 and HMGB1 were detected by RT-qPCR and Western blot.The pathological changes of intestinal tissue were detected by HE staining.CCK-8 assay determined the optimal treatment time of LPS.Caco-2 cells were transfected with NRIP1 small interfering RNA(siRNA-NRIP1-1/2),and cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.RT-qPCR and Western blot examined the expressions of inflammation-associated factors.Transepithelial resistance(TEER)was used to detect intestinal epi-thelial permeability.Western blot was used to detect the expressions of apoptosis and tight-junction related proteins.The binding rela-tionship between NRIP1 and HMGB1 was verified by luciferase reporting assay and chromatin immunoprecipitation assay(ChIP).After knocking down NRIP1 and overexpressing HMGB1 in LPS-treated Caco-2 cells,the functional experiment was performed again.Results:NRIP1 expression was fortified in the intestinal tissues of sepsis rats and LPS-treated Caco-2 cells.Interference with NRIP1 attenuated LPS-elicited Caco-2 cell viability injury,apoptosis,inflammatory response and barrier damage.Additionally,NRIP1 might activate HMGB1 expression at transcriptional level and HMGB1 elevation might reverse the impacts of NRIP1 absence on Caco-2 cell viability,apoptosis,inflammatory response as well as barrier function.Conclusion:NRIP1 may promote sepsis-elicited intestinal epi-thelial injury,which may be related to transcriptional activation of HMGB1.