Overexpression of bone morphogenetic protein receptor type 2 suppresses transforming growth factor β-induced profibrotic responses in lung fibroblasts.

Abstract

Materials and methods: We investigated BMPR2 expression in pulmonary fibrosis and TGF-β/BMP signaling in lung fibroblasts. Then we evaluated the impact of BMPR2 upregulation using adenoviral transduction on TGF-β-induced Smad2/3 phosphorylation and fibronectin production in lung fibroblasts.

Results: BMPR2 was distributed in airway epithelium and alveolar walls in rat lungs. BMPR2 expression was decreased in fibrotic lesions in the lungs of rats with bleomycin-induced pulmonary fibrosis and in human lung fibroblasts (HLFs) stimulated with TGF-β. Although Smad2/3 phosphorylation and fibronectin production were not suppressed solely by BMPs, phosphorylated Smad2/3 was decreased in BMPR2-transduced cells even without BMP stimulation. Fibronectin was decreased only when BMPR2-transduced HLFs were stimulated with BMP7 (but not BMP4). Similar results were also observed in IPF patient HLFs and rat lung fibroblasts.

Conclusions: BMPR2 expression was reduced in fibrotic lungs and lung fibroblasts stimulated with TGF-β. BMPR2 transduction to lung fibroblasts reduced Smad2/3 phosphorylation, and reduced fibronectin production when treated with BMP7. Upregulation of BMPR2 may be a possible strategy for treating pulmonary fibrosis.