Glycyrrhizic Acid Attenuates Pulmonary Fibrosis of Silicosis by Inhibiting the Interaction between HMGB1 and BRG1 through PI3K/Akt/mTOR Pathway

Zhuoya Niu, Jisong Lin, Changfu Hao, Xiao Xu, Chen Wang, Kai Dai, Xuedan Deng, Meng Deng, Yonghua Guo and Wu Yao
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Zhuoya Niu: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Jisong Lin: Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Changfu Hao: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Xiao Xu: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Chen Wang: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Kai Dai: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Xuedan Deng: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Meng Deng: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Yonghua Guo: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
Wu Yao: Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China

IJERPH, 2022, vol. 19, issue 14, 1-16

Abstract: Purpose: High mobility group protein 1 (HMGB1) is a highly conserved DNA-binding nuclear protein that participates in the occurrence and development of silicosis. HMGB1 binds to its specific receptor and activates phosphatidylinositol 3-kinase (PI3K)/protein kinase B, (PKB; Akt)/mammalian target of rapamycin (mTOR) pathway. Brahma-related genes 1 (BRG1; SMARCA4) is the core subunit of SWI/SNF. HMGB1 activates the Akt pathway through BRG1 to promote the proliferation of prostate cancer. Glycyrrhizic acid is a new pharmacological inhibitor of HMGB1, which may inhibit the occurrence and development of silicosis. We speculate that glycyrrhizic acid inhibits the interaction between HMGB1 and BRG1 through the PI3K/Akt/mTOR pathway to affect the progression of silicosis. Methods: We carried out an in vitro study and stimulated A549 with TGF-β1 to establish an epithelial–mesenchymal transition (EMT) model, knocked down the HMGB1 and BRG1 genes in cells, observed the expression of EMT markers, and detected the interaction between HMGB1 and BRG1 by co-immunoprecipitation. In vivo, we injected glycyrrhizic acid into the mouse silicosis model to inhibit the expression of HMGB1. Results: Both HMGB1 and BRG1 were highly expressed in the process of EMT. After knocking down HMGB1 and BRG1, the process of EMT was inhibited through the PI3K/Akt/mTOR pathway, and their expressions were influenced by each other. HMGB1 and BRG1 interact with each other in A549 cells. HMGB1 and BRG1 are also highly expressed in the mouse silicosis model, and glycyrrhizic acid can inhibit the expression of HMGB1/BRG1 through the PI3K/Akt/mTOR pathway. Conclusion: Glycyrrhizic acid can inhibit the interaction between HMGB1 and BRG1 through the PI3K/Akt/mTOR pathway to affect the progression of silicosis.

Keywords: HMGB1; BRG1; glycyrrhizic acid; silicosis; PI3K/Akt/mTOR signaling (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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