scholarly journals Postnatal Deletion of the Type II Transforming Growth Factor-β Receptor in Smooth Muscle Cells Causes Severe Aortopathy in Mice

2015 ◽  
Vol 35 (12) ◽  
pp. 2647-2656 ◽  
Author(s):  
Jie Hong Hu ◽  
Hao Wei ◽  
Mia Jaffe ◽  
Nathan Airhart ◽  
Liang Du ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Transforming Growth Factor ◽  
Muscle Cells ◽  
Transforming Growth Factor Β ◽  
Type Ii ◽  
Β Receptor

scholarly journals Transforming Growth Factor-β and Notch Signaling Mediate Stem Cell Differentiation into Smooth Muscle Cells

Stem Cells ◽  
2010 ◽  
Vol 28 (4) ◽  
pp. 734-742 ◽  
Author(s):  
Kyle Kurpinski ◽  
Hayley Lam ◽  
Julia Chu ◽  
Aijun Wang ◽  
Ahra Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Notch Signaling ◽  
Transforming Growth Factor ◽  
Stem Cell Differentiation ◽  
Muscle Cells ◽  
Transforming Growth Factor Β

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.

Sign in / Sign up

Export Citation Format

Share Document