Quercetin improves ESAT-۶-induced pleural mesothelial cell fibrosis by activating the NRF۲/HO-۱ pathway

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-۶ (ESAT-۶) by activating the Nrf۲/HO-۱ signaling pathway, thereby suppressing oxidative stress.Materials and Methods: An in vitro model of ESAT-۶-induced HPMC fibrosis was established. The effects of various concentrations of quercetin on HPMCs were assessed using the CCK-۸ 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 ۲-related factor ۲ (Nrf۲), and western blot analysis was conducted to evaluate the protein levels of Nrf۲, heme oxygenase-۱ (HO-۱), E-cadherin (E-cad), and α-smooth muscle actin (α-SMA).Results: Quercetin significantly improved ESAT-۶-induced HPMC proliferation, reduced the oxidative stress marker MDA, and decreased the fibrosis marker α-SMA levels. It also promoted the translocation of Nrf۲ into the nucleus in ESAT-۶-induced pleural mesothelial cell fibrosis. Furthermore, quercetin enhanced the enzymatic activity of antioxidants, particularly GSH and SOD, and increased the expression levels of HO-۱, Nrf۲, and E-cad.Conclusion: The findings indicate that quercetin can inhibit oxidative stress by modulating the Nrf۲ pathway and up-regulating HO-۱ activity, thereby improving ESAT-۶-induced pleural mesothelial cell fibrosis.

کلیدواژه ها:

ESAT-۶ ، Fibrosis ، HPMCs ، Nrf۲/HO-۱ ، Quercetin