BRD4 regulates alveolar epithelial-mesenchymal transition through HMGB1/TGF-β1/Smad pathway
10.19405/j.cnki.issn1000-1492.2025.02.009
- Author:
Ruru Chen
1
;
Lu Han
1
;
Hailan He
2
;
Xiaohui Hao
2
;
Heliang Liu
2
;
Lingli Guo
3
Author Information
1. School of Public Health , North China University of Science and Technology , Tangshan 063210
2. School of Public Health , North China University of Science and Technology , Tangshan 063210; Hebei Key Laboratory of Organ Fibrosis , Tangshan 063210
3. School of Public Health , North China University of Science and Technology , Tangshan 063210 ; College of Medical Technology , Chengdu University of Traditional Chinese Medicine , Chengdu 610075
- Publication Type:Journal Article
- Keywords:
BRD4;
HMGB1;
TGF-β1 /Smad2/3;
EMT;
fibrosis;
JQ-1
- From:
Acta Universitatis Medicinalis Anhui
2025;60(2):247-254
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells.
Methods : MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test.
Results :Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration.
Conclusion:BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.
- Full text:2026012210405740134BRD4通过HMGB1_T...与调控肺泡上皮细胞间质转化_陈茹茹.pdf
