Quercetin ameliorates epithelial-mesenchymal transition and inflammation by targeting FSTL1 and modulating the NF-κB Pathway in pulmonary fibrosis

CuiTing Dong^1,2YueJiao Lan^1*Mingda Wu¹Ruichen Yuan²Kunpeng Yang²Zhen Yang²Yang Chen²JingBin Zhang¹BingXue Qi^1*XiaoDan Lu^1*

• ¹The People's Hospital of Jilin Province, Changchun, Jilin Province, China
• ²Changchun University of Chinese Medicine, Changchun, Jilin Province, China

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.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.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.