title: Alpha2-antiplasmin is involved in the production of transforming growth factor beta1 and fibrosis.
abstract: BACKGROUND
  Fibrotic disease occurs in most tissues. Transforming growth factor (TGF)-beta is the major inducer of fibrosis. The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices. However, the detailed mechanism of how this system affects fibrosis remains unclear.
  
  
  RESULTS
  We examined experimental fibrosis in mice with a deficiency of alpha(2)-antiplasmin (alpha2AP), which is a potent and specific plasmin inhibitor. We found that the lack of alpha2AP attenuated bleomycin-induced TGF-beta(1) synthesis and fibrosis. In addition, the production of TGF-beta(1) from the explanted fibroblasts of alpha2AP(-/-) mice decreased dramatically as compared to that in wild-type mice. Moreover, we found that alpha2AP specifically induces the production of TGF-beta(1) in fibroblasts.
  
  
  CONCLUSIONS
  The lack of alpha2AP attenuated TGF-beta(1) synthesis, thereby resulting in attenuated fibrosis. This is the first report to describe the crucial role that alpha2AP plays in TGF-beta(1) synthesis during the process of fibrosis. Our results provide new insights into the role of alpha2AP in fibrosis.
authors.affiliation: Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, D.W.C.L.A., Kyoto, Japan. ykanno@dwc.doshisha.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kanno
authors.forename: A
authors.initials: A
authors.lastname: Kuroki
authors.forename: K
authors.initials: K
authors.lastname: Okada
authors.forename: K
authors.initials: K
authors.lastname: Tomogane
authors.forename: S
authors.initials: S
authors.lastname: Ueshima
authors.forename: O
authors.initials: O
authors.lastname: Matsuo
authors.forename: H
authors.initials: H
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D001761:Bleomycin; D002478:Cells, Cultured; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*; D000979:alpha-2-Antiplasmin / Q000172:deficiency / Q000502:physiology*
chemical_list: D053773:Transforming Growth Factor beta1; D000979:alpha-2-Antiplasmin; D001761:Bleomycin