Platelet-Derived Growth Factor Induced Alpha-Smooth Muscle Actin Expression by Human Retinal Pigment Epithelium Cell

2013 ◽  
Vol 29 (3) ◽  
pp. 310-318 ◽  
Author(s):  
Yanfang Si ◽  
Jun Wang ◽  
Juan Guan ◽  
Quanhong Han ◽  
Yannian Hui
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Actin ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelium Cell ◽  
Platelet Derived Growth Factor ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Actin Expression

scholarly journals The RhoA Activator GEF-H1/Lfc Is a Transforming Growth Factor-β Target Gene and Effector That Regulates α-Smooth Muscle Actin Expression and Cell Migration

2010 ◽  
Vol 21 (6) ◽  
pp. 860-870 ◽  
Author(s):  
Anna Tsapara ◽  
Phillip Luthert ◽  
John Greenwood ◽  
Caroline S. Hill ◽  
Karl Matter ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Muscle Actin ◽  
Rpe Cells ◽  
A Genome

Maintenance of the epithelial phenotype is crucial for tissue homeostasis. In the retina, dedifferentiation and loss of integrity of the retinal pigment epithelium (RPE) leads to retinal dysfunction and fibrosis. Transforming growth factor (TGF)-β critically contributes to RPE dedifferentiation and induces various responses, including increased Rho signaling, up-regulation of α-smooth muscle actin (SMA), and cell migration and dedifferentiation. Cellular TGF-β responses are stimulated by different signal transduction pathways: some are Smad dependent and others Smad independent. Alterations in Rho signaling are crucial to both types of TGF-β signaling, but how TGF-β-stimulates Rho signaling is poorly understood. Here, we show that primary RPE cells up-regulated GEF-H1 in response to TGF-β. GEF-H1 was the only detectable Rho exchange factor increased by TGF-β1 in a genome-wide expression analysis. GEF-H1 induction was Smad4-dependant and led to Rho activation. GEF-H1 inhibition counteracted α-SMA up-regulation and cell migration. In patients with retinal detachments and fibrosis, migratory RPE cells exhibited increased GEF-H1 expression, indicating that induction occurs in diseased RPE in vivo. Our data indicate that GEF-H1 is a target and functional effector of TGF-β by orchestrating Rho signaling to regulate gene expression and cell migration, suggesting that it represents a new marker and possible therapeutic target for degenerative and fibrotic diseases.

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