Integrin α8β1 mediates adhesion to LAP-TGFβ1

摘要: The development of fibrosis is a common response to variety injuries and results in the net accumulation matrix proteins and impairment of normal organ function. We previously reported that integrinα 8β1 expressed by alveolar interstitial cells normal lung and is upregulated during fibrosis. TGFβ1 an important mediator inflammatory pulmonary is secreted as latent protein non-covalently associated with latency-associated peptide (LAP) requires activation exert its effects. LAP-TGFβ1 LAP-TGFβ3 contain tripeptide sequence, arginine-glycine-aspartic acid (RGD), known integrin recognition motif. The integrin α8β1 binds several ligands such fibronectin and vitronectin through RGD sequence. Recent reports demonstrate the integrins αvβ1, αvβ6 αvβ8 adhere to LAP-TGFβ1 site. Therefore, we asked whether LAP-TGFβ1 might be ligand for whether this may be important found cell lines transfected with α8 subunit were able spread on recombinant LAP-TGFβ1 significantly better than mock transfected lines.α 8-transfected also LAP-TGFβ3 significantly cells. Adhesion LAP-TGFβ1 was enhanced Mn 2+ , or 8A2, an integrin β1 activating antibody. Furthermore, adhesion was abolished when used recombinant LAP-TGFβ1 which site was mutated RGE. binding increased cell proliferation phosphorylation FAK ERK, but did not activate of TGFβ1. These data strongly suggest ofα 8β1 interaction with may influence behavior.