Quercetin improves ESAT-6-induced pleural mesothelial cell fibrosis by activating the NRF2/HO-1 pathway

Articles in Press

Document Type : Original Article

Authors

1 Department of Tuberculosis, Guiyang Public Health Clinical Center, Guiyang, Guizhou, China

2 Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China

3 Department of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China

4 Department of Pathology, Guiyang Public Health Clinical Center, Guiyang, Guizhou, China

5 Department of Respiratory and Critical Care Medicine, The Fourth People’s Hospital of Guiyang, Guiyang, Guizhou, China

6 Department of Infectious Diseases, Guiyang Public Health Clinical Center, Guiyang, Guizhou, China

10.22038/ijbms.2026.86824.18778

Abstract

Objective(s): This study investigated the mechanism by which quercetin suppresses oxidative stress and improves fibrosis in human pleural mesothelial cells (HPMCs) induced by the Mycobacterium tuberculosis-specific antigen early secretory antigen target protein-6 (ESAT-6) by activating the Nrf2/HO-1 signaling pathway, thereby suppressing oxidative stress.
Materials and Methods: An in vitro model of ESAT-6-induced HPMC fibrosis was established. The effects of various concentrations of quercetin on HPMCs were assessed using the CCK-8 assay. Markers of oxidative stress, such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH), were assessed. Immunofluorescence was utilized to detect levels of nuclear factor erythroid 2-related factor 2 (Nrf2), and western blot analysis was conducted to evaluate the protein levels of Nrf2, heme oxygenase-1 (HO-1), E-cadherin (E-cad), and α-smooth muscle actin (α-SMA).
Results: Quercetin significantly improved ESAT-6-induced HPMC proliferation, reduced the oxidative stress marker MDA, and decreased the fibrosis marker α-SMA levels. It also promoted the translocation of Nrf2 into the nucleus in ESAT-6-induced pleural mesothelial cell fibrosis. Furthermore, quercetin enhanced the enzymatic activity of antioxidants, particularly GSH and SOD, and increased the expression levels of HO-1, Nrf2, and E-cad.
Conclusion: The findings indicate that quercetin can inhibit oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby improving ESAT-6-induced pleural mesothelial cell fibrosis.

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References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 27 April 2026

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