Figure 1.

Associated cell signaling pathway and related potential therapeutic areas. Integrin avβ6 interacts with the amino acid sequence RGD, which is located near the C-terminus of LAP. TGF-β can be activated after release from LAP. The inhibition of avβ6-mediated TGF-β activation prevents RIPF. Both LY2109761, a small molecule TGF-β receptor 1 serine/threonine kinase inhibitor, and galunisertib, a highly selective inhibitor of TGFβR1, attenuate RIPF by inhibiting TGF-β–associated downstream targets. Further, 2-methoxyestradiol (2-ME) effectively inhibits the action of HIF-1α, reducing EndMT, EMT, and concomitant deposition of vascular collagen and eventually attenuating the development of RIPF. PDGF receptor tyrosine kinase inhibitors (imatinib, SU9518, and SU11657) markedly attenuated the development of fibroblast foci and subsequent remodeling of lung architecture.