徳島大学 教育・研究者情報データベース(EDB)

1. 香美 祥二([徳島大学])

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2. 近藤 秀治

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3. (英) Loster Klemens

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4. (英) Reutter Werner

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5. (英) Kuhara Takashi

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6. 安友 康二([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.生体防御医学])

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7. 黒田 𣳾弘

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(英) Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells is differentially regulated by transforming growth factor-beta and platelet-derived growth factor-BB

(英) Pathologic remodeling of mesangial matrix after glomerular injury is the central biologic feature of glomerular scarring (sclerosis). Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB have been implicated in the development of glomerular scarring in rat and human glomerulonephritis. To clarify molecular and cellular mechanisms involved in abnormal mesangial remodeling, this study focused on the role of alpha1beta1 integrin, a collagen/laminin receptor, in rat mesangial cells, using collagen gel contraction as an experimental model of in vivo collagen matrix remodeling and scar formation. In addition, the influence of TGF-beta and PDGF-BB on mesangial cell (MC)-mediated collagen gel contraction in association with the alpha1beta1 integrin expression was evaluated. Integrin function blocking studies using anti-alpha1, beta1 subunit antibodies indicated that MC-alpha1beta1 integrin is essentially required not only for collagen-dependent adhesion/migration, but also for gel contraction. Protein synthesis and mRNA analysis experiments demonstrated that TGF-beta, but not PDGF-BB, increases the expression of alpha1beta1 integrin in mesangial cells cultured on plastic surface and in collagen gels. The upregulation of alpha1beta1 integrin expression by TGF-beta correlated with increases in gel contraction and collagen-dependent adhesion but not migration of mesangial cells. On the other hand, PDGF-BB enhanced MC-mediated gel contraction and migration without affecting cell adhesion to collagen I. Growth factor-induced collagen-dependent adhesion, migration, and gel contraction were significantly attenuated by incubation with anti-alpha1, beta1 subunit antibodies. Thus, these data indicate that alpha1beta1 integrin-mediated collagen matrix remodeling can be modulated by TGF-beta and PDGF-BB via different mechanisms. Alpha1 integrin-mediated mesangial matrix remodeling induced by TGF-beta or PDGF-BB may be a pathogenic mechanism leading to glomerular scarring.

1. (英) Animals
2. (英) Blotting, Northern
3. (英) Cell Adhesion
4. (英) Cell Movement
5. (英) Cells, Cultured
6. コラーゲン(collagen)
7. (英) Disease Models, Animal
8. 細胞外マトリックス(extracellular matrix)
9. (英) Glomerular Mesangium
10. (英) Humans
11. 免疫組織化学(immunohistochemistry)
12. (英) Integrin alpha1beta1
13. (英) Integrins
14. (英) Platelet-Derived Growth Factor
15. (英) Rats
16. (英) Rats, Sprague-Dawley
17. (英) Reference Values
18. (英) Transforming Growth Factor beta

1. (英) Article.PublicationTypeList.PublicationType: Comparative Study

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't