Downregulated expression of integrin alpha6 by transforming growth factor-beta(1) on lens epithelial cells in vitro.
Integrins represent the main cell surface receptors that mediate cell-matrix and cell-cell interactions. They play critical roles in adhesion, migration, morphogenesis, and the differentiation of several cell types. Previous studies have demonstrated that members of the fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-beta(1), and insulin growth factor (IGF)-1 play important roles in lens biology. In particularly, TGF-beta(1) appears to play a key role in extracellular matrix production, cell proliferation, and cell differentiation of lens epithelial cells. In this study we investigated the effects of FGF-2, TGF-beta(1), and IGF-1 on the modulation of integrin receptors using lens epithelial cell lines (HLE B-3 and alphaTN-4) and lens explants. We found that the expression of integrin alpha6 is downregulated by TGF-beta(1), but is not responsive to FGF-2 or IGF-1. The promoter activity of the integrin alpha6 gene decreased upon TGF-beta(1) treatment in a transient transfection assay, and flow cytometric analysis demonstrated the reduced expression of integrin alpha6 by TGF-beta(1), whereas significant changes were not observed in the level of integrin alpha6 after the addition of FGF-2. These findings suggest that the reduced expression of integrin alpha6 caused by TGF-beta(1) might play a role in the activation of the cell cycle genes required during the fiber differentiation of the lens.
Lim
J M
JM
Department of Ophthalmology and Visual Science, College of Medicine, Catholic University of Korea, and Catholic Research Institutes of Medical Sciences, Seoul, Korea.
Kim
J A
JA
Lee
J H
JH
Joo
C K
CK
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D039482:Integrin alpha5; D039503:Integrin alpha6; D039564:Integrin alphaV; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D015703:Antigens, CD; D039482:Integrin alpha5; D039503:Integrin alpha6; D039564:Integrin alphaV; D007797:Laminin; D020033:Protein Isoforms; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I