Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB pathway in pulmonary fibrosis
Yuejiao Lan, Cuiting Dong, Mingda Wu, Ren Yuan, Kunpeng Yang, Zhen Yang, Yang Chen, Jingbin Zhang, Bingxue Qi, Xiaodan Lu
Abstract
Background Idiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by chronic inflammation and pathological lung remodeling driven by excessive extracellular matrix deposition. While the flavonol quercetin exhibits established anti-inflammatory and antioxidant properties, its therapeutic mechanisms against IPF—particularly regarding epithelial-mesenchymal transition (EMT) and inflammation regulation via the follistatin-like 1 (FSTL1)/nuclear factor kappa B (NF-κB) axis—remain incompletely elucidated. This study therefore investigates quercetin’s capacity to mitigate pulmonary fibrosis through targeted modulation of the FSTL1/NF-κB pathway. Methods A bleomycin (BLM)-induced pulmonary fibrosis mouse model and Transforming Growth Factor Beta 1 (TGF-β1)-induced EMT models in A549 and BEAS-2B cells were employed. The therapeutic effects of quercetin were assessed through H&E, Masson, Sirius red staining, immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of FSTL1 and NF-κB signaling in the anti-fibrotic effects of quercetin was evaluated using FSTL1 knockdown. Results In vivo studies have shown that BLM-induced pulmonary fibrosis and inflammation significantly increased the deposition of extracellular matrix and the levels of interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6), all of which were markedly reduced by quercetin administration. In vitro experiments revealed that quercetin suppressed TGF-β1-induced EMT and inflammation. Importantly, FSTL1 knockdown diminished the anti-inflammatory and anti-EMT effects of quercetin. Conclusion Quercetin exerts its protective effects against pulmonary fibrosis by suppressing FSTL1 expression and modulating the NF-κB signaling pathway, thereby inhibiting both inflammation and EMT process.