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In this study we analyzed how blocking TGF\u03b2 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 TGF\u03b2 signaling in the Fra-2 Tg mice, we used a pan-TGF\u03b2-blocking antibody, 1D11, and Tg mice in which TGF\u03b2 receptor type 2 ( Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (\u03b1-SMA-Cre<jats:sup>ER<\/jats:sup>; Tgfbr2<jats:sup>flox\/flox<\/jats:sup>). Global inhibition of TGF\u03b2 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 TGF\u03b2 signaling contributes to development of pulmonary vascular remodeling by promoting the proliferation of vascular smooth muscle cells. Deletion of Tgfbr2 from \u03b1-smooth muscle actin-expressing cells had no effect on fibrosis or inflammation in this model. These results suggest that efforts to target TGF\u03b2 in SSc will likely require more precision than simply global inhibition of TGF\u03b2 function.<\/jats:p>","DOI":"10.1152\/ajplung.00428.2016","type":"journal-article","created":{"date-parts":[[2016,11,19]],"date-time":"2016-11-19T02:50:32Z","timestamp":1479523832000},"page":"L22-L31","source":"Crossref","is-referenced-by-count":30,"title":["Transforming growth factor-\u03b2 plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma"],"prefix":"10.1152","volume":"312","author":[{"given":"Kazuyuki","family":"Tsujino","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilgun Isik","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, 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