scholarly journals HIV-1 Tat-Mediated Induction of Platelet-Derived Growth Factor in Astrocytes: Role of Early Growth Response Gene 1

2011 ◽  
Vol 186 (7) ◽  
pp. 4119-4129 ◽  
Author(s):  
Crystal Bethel-Brown ◽  
Honghong Yao ◽  
Shannon Callen ◽  
Young Han Lee ◽  
Prasanta K. Dash ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Response ◽  
Early Growth ◽  
Platelet Derived Growth Factor ◽  
Response Gene ◽  
Early Growth Response ◽  
Early Growth Response Gene ◽  
Hiv 1

scholarly journals Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis

2004 ◽  
Vol 200 (3) ◽  
pp. 377-389 ◽  
Author(s):  
Chun Geun Lee ◽  
Soo Jung Cho ◽  
Min Jong Kang ◽  
Svetlana P. Chapoval ◽  
Patty J. Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Response ◽  
Transforming Growth Factor ◽  
Early Growth ◽  
Transient Wave ◽  
Response Gene ◽  
Early Growth Response ◽  
Early Growth Response Gene ◽  
Tgf Β1

Fibrosis and apoptosis are juxtaposed in pulmonary disorders such as asthma and the interstitial diseases, and transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of these responses. However, the in vivo effector functions of TGF-β1 in the lung and its roles in the pathogenesis of these responses are not completely understood. In addition, the relationships between apoptosis and other TGF-β1–induced responses have not been defined. To address these issues, we targeted bioactive TGF-β1 to the murine lung using a novel externally regulatable, triple transgenic system. TGF-β1 produced a transient wave of epithelial apoptosis that was followed by mononuclear-rich inflammation, tissue fibrosis, myofibroblast and myocyte hyperplasia, and septal rupture with honeycombing. Studies of these mice highlighted the reversibility of this fibrotic response. They also demonstrated that a null mutation of early growth response gene (Egr)-1 or caspase inhibition blocked TGF-β1–induced apoptosis. Interestingly, both interventions markedly ameliorated TGF-β1–induced fibrosis and alveolar remodeling. These studies illustrate the complex effects of TGF-β1 in vivo and define the critical role of Egr-1 in the TGF-β1 phenotype. They also demonstrate that Egr-1–mediated apoptosis is a prerequisite for TGF-β1–induced fibrosis and remodeling.

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