This study investigates the role of miR-21 in the pathogenesis and progression of lung fibrosis. The authors found that miR-21 is up-regulated in the lungs of mice with bleomycin-induced fibrosis and in patients with idiopathic pulmonary fibrosis (IPF). MiR-21 expression is primarily localized to myofibroblasts, which are key cells in the fibrotic process. TGF-β1, a central mediator of fibrotic diseases, enhances miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promotes the pro-fibrogenic activity of TGF-β1, while knocking down miR-21 attenuates this effect. The mechanism involves regulation of Smad7, an inhibitory Smad, by miR-21. Inhibition of miR-21 with antisense probes prevents experimental lung fibrosis in mice, suggesting a potential therapeutic approach for treating fibrotic diseases like IPF.This study investigates the role of miR-21 in the pathogenesis and progression of lung fibrosis. The authors found that miR-21 is up-regulated in the lungs of mice with bleomycin-induced fibrosis and in patients with idiopathic pulmonary fibrosis (IPF). MiR-21 expression is primarily localized to myofibroblasts, which are key cells in the fibrotic process. TGF-β1, a central mediator of fibrotic diseases, enhances miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promotes the pro-fibrogenic activity of TGF-β1, while knocking down miR-21 attenuates this effect. The mechanism involves regulation of Smad7, an inhibitory Smad, by miR-21. Inhibition of miR-21 with antisense probes prevents experimental lung fibrosis in mice, suggesting a potential therapeutic approach for treating fibrotic diseases like IPF.