To investigate whether HIF pathway activation acts as a mechanism that drives pathologic collagen crosslinking by disproportionate induction of collagen-modifying enzymes relative to TGFβ-induced collagen fibril synthesis, we employed our long-term (6 weeks) 3D in vitro model of lung fibrosis using primary human lung fibroblasts from patients with IPF, which we have previously described (Jones et al., 2018) and which allows direct evaluation of pyridinoline cross-linking, collagen nanostructure, and tissue biomechanics. This evidence concerns the gene TGFB1 and pulmonary fibrosis.