Investigation of mechanism of pulmonary fibrosis focusing on post-translational modification of osteopontin and its receptor change

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We investigated mechanism of pulmonary fibrosis focusing on post-translational modifications of osteopontin and associating receptor change.1) Osteopontin was polymerized by transglutaminase 2.2) Cell adhesion, spreading, and migration were enhanced when cells were plated on polymeric osteopontin than on monomeric osteopontin.3) Focal contact formation in cells plated on polymeric osteopontin was dramatic, which suggests the cell behaviors described above were mediated by integrin receptors.4) Polymeric osteopontin induces neutrophil migration in vitro, which was analyzed by horizontal migration analysis apparatus, Taxiscan.5) Polymeric osteopontin recruited neutrophils into mouse peritoneal space.These results suggest that polymerization of osteopontin is involved in lung injury induced by neutrophils, the first step of pulmonary fibrosis. Although we could not describe in this report, we are on a process of generating osteopontin mutant mice to confirm the effects of polymerization of osteopontin on pulmonary fibrosis.