The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis
J S Munger, X Huang, H Kawakatsu, M J Griffiths, S L Dalton, J Wu, J F Pittet, N Kaminski, C Garat, M A Matthay, D B Rifkin, D Sheppard, J S Munger, X Huang, H Kawakatsu, M J Griffiths, S L Dalton, J Wu, J F Pittet, N Kaminski, C Garat, M A Matthay, D B Rifkin, D Sheppard
Abstract
Transforming growth factor beta (TGF beta) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGF beta gene product. Extracellular activation of these complexes is a critical but incompletely understood step in regulation of TGF beta function in vivo. We show that TGF beta 1 LAP is a ligand for the integrin alpha v beta 6 and that alpha v beta 6-expressing cells induce spatially restricted activation of TGF beta 1. This finding explains why mice lacking this integrin develop exaggerated inflammation and, as we show, are protected from pulmonary fibrosis. These data identify a novel mechanism for locally regulating TGF beta 1 function in vivo by regulating expression of the alpha v beta 6 integrin.
Source: PubMed