Luteolin Modulates miRNA–mRNA Regulatory Networks to Attenuate TGF-β1-Induced Fibrogenesis: Insights from Next-Generation Sequencing

Luteolin has demonstrated therapeutic potential against pulmonary fibrosis, yet the underlying miRNA-mediated regulatory mechanisms remain poorly defined. In this study, we employed next-generation sequencing to explore the effects of luteolin on TGF-β1-induced fibrogenesis in MRC5 cells, with a focus on miRNA–mRNA interactions. Real-time PCR analysis confirmed that luteolin pretreatment significantly suppressed TGF-β1-induced expression of key fibrotic markers, including TGFB1, ACTA2, COL1A1, and FN1, indicating a potent anti-fibrotic effect. Transcriptomic profiling revealed that luteolin reversed the expression of 692 genes dysregulated by TGF-β1, with functional enrichment analyses highlighting significant pathways related to cellular movement and localization. Furthermore, integrated miRNA–mRNA network analysis identified eight negatively correlated pairs potentially involved in these processes. These findings provide new insights into the anti-fibrotic mechanisms of luteolin and underscore the role of miRNA–mRNA regulatory networks in pulmonary fibrosis. This study enhances our molecular understanding of fibrogenesis and supports the potential of luteolin as a modulator of post-transcriptional gene regulation in fibrosis. RNA-seq and small RNA-seq of control, TGF-β1 treatment, and luteolin plus TGF-β1 treatment in MRC5 cell line.