However, studies in several mouse models have shown that vascular remodeling can occur independently of hypoxia and precede the development of bleomycin-induced PF, Fra-2–induced SSc-ILD, and tobacco smoke–induced emphysema (60–63), suggesting that vascular alterations might play a more active role in the progression of underlying lung diseases than previously believed. The gene discussed is FOSL2; the disease is systemic sclerosis.