title: Blocking of alpha 5 integrin stimulates production of TGF-beta and PAI-1 by human mesangial cells.
abstract: Expression of integrin, which mediates cell-matrix interaction, is affected by several cytokines, in particular by transforming growth factor-beta (TGF-beta). However, it is unknown whether, in an opposite way, a specific integrin is involved in cytokine synthesis. We tested this hypothesis. Function-blocking anti-alpha 5 integrin (fibronectin receptor) antibody increased TGF-beta secretion in growth-arrested human mesangial cells (2.3-fold) compared with control IgG or anti-alpha v beta 3 integrin (receptor for several matrix proteins) antibody. It also increased the secretion of plasminogen activator inhibitor-1 (PAI-1), a protein associated with matrix increase, by 3.2-fold. The increase in PAI-1 secretion induced by anti-alpha 5 integrin antibody was not abrogated by anti-TGF-beta neutralizing antibody. These results indicate that function-blocking of anti-alpha 5 integrin stimulates TGF-beta as well as PAI-1 production, suggesting that alpha 5 integrin is involved in fibrotic process. Function-modulation of a specific integrin thus appears to play a role in glomerular remodeling.
authors.affiliation: Department of Nephrology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Ishimura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shioi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D039482:Integrin alpha5 / Q000276:immunology / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D000906:Antibodies; D039482:Integrin alpha5; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta