Transforming growth factor-β: a growth factor inducing αB-crystallin expression in ciliary muscle cells

2000 ◽  
Vol 238 (12) ◽  
pp. 993-997 ◽  
Author(s):  
Ulrich Welge-Lüßen ◽  
Hans Bloemendal ◽  
E. Lütjen-Drecoll
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Muscle Cells ◽  
Transforming Growth Factor Β ◽  
Ciliary Muscle ◽  
Αb Crystallin

scholarly journals Transforming growth factor-β plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma

2017 ◽  
Vol 312 (1) ◽  
pp. L22-L31 ◽  
Author(s):  
Kazuyuki Tsujino ◽  
Nilgun Isik Reed ◽  
Amha Atakilit ◽  
Xin Ren ◽  
Dean Sheppard
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Vascular Remodeling ◽  
Transforming Growth Factor ◽  
Muscle Cells ◽  
Transforming Growth Factor Β ◽  
Tgfβ Signaling ◽  
Pulmonary Vascular Remodeling ◽  
Global Inhibition

The efficacy and feasibility of targeting transforming growth factor-β (TGFβ) in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study we analyzed how blocking TGFβ signaling affects pulmonary abnormalities in Fos-related antigen 2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGFβ signaling in the Fra-2 Tg mice, we used a pan-TGFβ-blocking antibody, 1D11, and Tg mice in which TGFβ receptor type 2 ( Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-CreER; Tgfbr2 flox/flox). Global inhibition of TGFβ by 1D11 did not ameliorate lung fibrosis histologically or biochemically, whereas it resulted in a significant increase in the number of immune cells infiltrating the lungs. In contrast, 1D11 treatment ameliorated the severity of pulmonary vascular remodeling in Fra-2 Tg mice. Similarly, genetic deletion of Tgfbr2 from smooth muscle cells resulted in improvement of pulmonary vascular remodeling in the Fra-2 Tg mice, as well as a decrease in the number of Ki67-positive vascular smooth muscle cells, suggesting that TGFβ signaling contributes to development of pulmonary vascular remodeling by promoting the proliferation of vascular smooth muscle cells. Deletion of Tgfbr2 from α-smooth muscle actin-expressing cells had no effect on fibrosis or inflammation in this model. These results suggest that efforts to target TGFβ in SSc will likely require more precision than simply global inhibition of TGFβ function.

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