Danthron Targets GRIM-12 to Alleviate Oxidative Stress and Inflammation in COPD Through Activation of Nrf2/HO-1 Pathway
10.3870/j.issn.1672-0741.24.12.014
- VernacularTitle:Danthron通过靶向GRIM-12影响Nrf2/HO-1通路缓解COPD中的氧化应激和炎症反应
- Author:
Xiaojie WU
1
;
Shuo YANG
1
;
Gan ZHA
1
Author Information
1. 华中科技大学同济医学院附属武汉中西医结合医院,武汉市第一医院呼吸与危重症医学科,武汉 430022
- Publication Type:Journal Article
- Keywords:
chronic obstructive pulmonary disease;
GRIM-12;
Danthron;
oxidative stress;
Nrf2/HO-1 signaling pathway;
lipid metabolism;
inflammatory response
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(1):1-7
- CountryChina
- Language:Chinese
-
Abstract:
Objective Chronic obstructive pulmonary disease(COPD)is a global respiratory disorder characterized by chron-ic inflammation and airflow limitation.Dysregulation of lipid metabolism plays a pivotal role in its progression.This study aimed to explore the expression of the lipid metabolism-related gene GRIM-12 in COPD,and assess the therapeutic potential of its in-hibitor,Danthron.Methods Gene expression datasets GSE10006 and GSE11784 from the Gene Expression Omnibus(GEO)were analyzed to identify GRIM-12 as a lipid metabolism-related gene upregulated in the small airway epithelium(SAE)of COPD patients.Human airway epithelial cells(16HBE)were stimulated in vitro with cigarette smoke extract(CSE)to evaluate GRIM-12 expression and the regulatory effects of Danthron.IL-6 level was assessed by using enzyme-linked immunosorbent assay(ELISA),while reactive oxygen species(ROS)level was quantified via fluorescence probe assays.The involvement of the Nrf2/HO-1 signaling pathway was also investigated.Results GRIM-12 expression was significantly upregulated in the SAE of COPD patients and in CSE-treated 16HBE cells.Molecular docking analysis showed that Danthron had a high binding affinity with GRIM-12,and inhibited its function through hydrogen bonding and hydrophobic interaction.Danthron treatment significantly suppressed CSE-induced GRIM-12 overexpression in v itro,reduced IL-6 secretion,and attenuated ROS production,alleviated oxidative stress and inflammatory responses.Mechanistic studies further revealed that Danthron enhanced cellular antioxidant defenses by activating Nrf2/HO-1 signaling pathway,thereby mitigating CSE-induced oxidative damage and inflammation.It is proved that Danthron regulated COPD-related pathological changes by targeting and inhibiting GRIM-12 expression.Conclusion Danthron effectively alleviates oxidative stress and inflammation in COPD by GRIM-12 expression inhibition and Nrf2/HO-1 signaling pathway activation,offering a promising therapeutic strategy for COPD management.
