Extracellular matrix production regulation by TGF-beta in corneal endothelial cells.
Invest Ophthalmol Vis Sci
; 39(11): 1981-9, 1998 Oct.
Article
em En
| MEDLINE
| ID: mdl-9761276
ABSTRACT
PURPOSE:
Production of extracellular matrix (ECM) by corneal endothelial cells is related to physiologic functions and pathologic conditions and is regulated by many cytokines, including transforming growth factor-beta (TGF-beta). In this study, the molecular mechanism of ECM production regulation by TGF-beta was investigated in cultured corneal endothelial cells.METHODS:
The production of ECM components (laminin and fibronectin) was detected in cultured corneal endothelial cells by western blot analysis. To determine the signal transduction pathways, mutant TGF-beta type I receptor (TbetaR-I) and/or Smad protein family members (intracellular signal transducers in TGF-beta signaling) were overexpressed by transfecting their cDNA into the cultured cells, and the effects on ECM production were observed.RESULTS:
The production of laminin and fibronectin was stimulated by treatment with TGF-beta1 or TGF-beta2. After transient transfection of cDNA of the constitutively active (CA) mutant of TbetaR-I, the production of laminin and fibronectin was stimulated even in the absence of TGF-beta. The transfection of the dominant negative mutant of TbetaR-I counteracted the effects of TGF-beta. These results confirm that TGF-beta directly stimulates ECM production from corneal endothelial cells through TbetaR-I. The ECM production stimulation by TGF-beta or CA TbetaR-I was accelerated by the overexpression of Smad2, Smad3, and/or Smad4 and inhibited by that of Smad7. These results show that TGF-beta signals connected to ECM production are regulated by Smad family members, located downstream of TbetaR-I.CONCLUSIONS:
The results of this study show that TGF-beta stimulates ECM production from corneal endothelial cells through TbetaR-I and Smad family transducers.
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Base de dados:
MEDLINE
Assunto principal:
Endotélio Corneano
/
Fator de Crescimento Transformador beta
/
Fibronectinas
/
Laminina
/
Matriz Extracelular
Limite:
Animals
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article