Sulforaphane attenuates lung fibrosis in bleomycin-induced pulmonary fibrosis via inhibition of TGF-β/Smad signaling

Sulforaphane(SFN) is a isothiocyanate that has chemoproventive, anti-inflammatory effects via NF-E2-related factor2 (Nrf2)-mediated induction of antioxidant/phase II enzymes. We evaluated the effects of sulforaphane on pulmonary fibrosis and profibrotic TGF-β/Smad signaling. Sulforaphane inhibited TGF-β-induced expression of fibronectin and collagen I in human pulmonary fibroblast cell lines (MRC-5 cells). Sulforaphane suppressed TGF-β-induced phosphorylation of Smad2/3. C57BL/6 male-gender mice in each group (control, BLM, BLM+SFN) were treated with BLM or SFN for 4 weeks. And then mice lungs were analyzed with histology (H&E, trichrome stain), western blot for TGF-β, fibronectin. The histological changes demonstrated that BLM instillation induced severe destruction of lung structure and accumulation of collagen in mice lungs. SFN treatment attenuated BLM-induced fibrotic lesions and collagen accumulation (hydroxyproline assay) in mice lungs. BLM increased TGF-β and fibronectin protein expression in lung tissues which was downregulated by SFN treatment. These findings suggest SFN treatment attenuates pulmonary fibrosis via inhibition of TGF-β/Smad signaling.