Effect of Quercetin on the Expression of NOXs and P-Smad3C in TGF-Β-Activated Hepatic Stellate Cell Line LX-2

Abstract

Background: Hepatic stellate cells (HSCs) play a primary role in liver fibrogenesis. NOXs are the main origin of reactive oxygen species (ROS) in the liver. Among them, NOX1, NOX2, and NOX4 are expressed more in HSCs and are involved in the development of liver fibrosis. Quercetin, an abundant citrus flavonoid, is known to have beneficial effects on liver injury and hepatic fibrosis. Objectives: In this study, the effect of quercetin on NOX1, NOX2, and NOX4 expression and Smad3 phosphorylation induced by TGF-β in the human hepatic LX2 cell line was investigated. Methods: The cytotoxic effects of quercetin on the cells were determined by MTT assay. The cells were activated with 2 ng/mL of TGF-β for 24 h and then treated with different concentrations of Quercetin. The mRNA expression rates of NOX1, NOX2, NOX4, and phosphorylated Smad 3C (p-Smad3C) were analyzed using real-time polymerase chain reaction (PCR) and western blot assays. Results: TGF-β increased the mRNA expression of NOX1, NOX2, and NOX4 and the protein level of p-Smad3C in the LX2 cell line. Quercetin significantly decreased the mRNA expression of NOX1, NOX2, and NOX4 in the LX-2 cells. Moreover, quercetin significantly diminished the p-Smad3C level in the LX-2 cell line activated with TGF-β. Conclusions: Quercetin may be effective in improving hepatic fibrosis via the reduction of NOX1, NOX2, and NOX4 expression in activated HSCs. The main mechanism through which quercetin reduces the expression of these target genes may be related to the reduction of the p-Smad3C level.

The Effect of Physalis angulata L. Administration on Gene Expressions Related to Lung Fibrosis Resolution in Mice-Induced Bleomycin

“…25,37 These findings align with Mohammadtaghvaei et al Quercetin led to a significant decrease in the mRNA expression of NOX4 induced by TGF-β in Hepatic Stellate Cell Line LX-. 22 Quercetin inhibits the process of macrophage transition both in vivo and in vitro, consequently attenuating the MMT and the TGF-β-Smad2/3 signaling pathway. Quercetin reduces scarring and inflammation in mice with lung damage caused by Bleomycin by making the antioxidant enzyme Nrf2.…”

“…Quercetin significantly suppressed TGF-β induced NOX4 mRNA expression. 22 TGF-β1 triggers NOX4 expression in lung mesenchymal cells via a SMAD3-dependent mechanism, leading to hydrogen peroxide (H2O2) generation essential for myofibroblast differentiation, ECM production, and contractility. High Nox4 expression induces fibroblast differentiation into myofibroblasts, triggering significant collagen secretion and ultimately leading to PF.…”

“…NOX4 plays a vital role in myofibroblast activation and lung fibroblast phenotype regulation. 22 Elevated Nox4 expression induces fibroblast differentiation into myofibroblasts, resulting in substantial collagen secretion and pulmonary fibrosis. Ciplukan extract inhibits radiation-induced fibroblast differentiation into myofibroblasts by targeting the p38/MAPK/Akt/Nox4 pathway, regulating mitochondrial ROS and ATP production.…”