| First Author | Tang YJ | Year | 2014 |
| Journal | Am J Respir Cell Mol Biol | Volume | 51 |
| Issue | 6 | Pages | 761-71 |
| PubMed ID | 24885478 | Mgi Jnum | J:232229 |
| Mgi Id | MGI:5776338 | Doi | 10.1165/rcmb.2013-0423OC |
| Citation | Tang YJ, et al. (2014) Latent transforming growth factor-beta1 protects against bleomycin-induced lung injury in mice. Am J Respir Cell Mol Biol 51(6):761-71 |
| abstractText | Transforming growth factor (TGF)-beta1 is a potent mediator known to induce lung fibrosis. However, the role of latent TGF-beta1 in lung inflammation and fibrosis is unclear. To investigate the role of circulating latent TGF-beta1 in bleomycin-induced lung injury, lung disease was induced in keratin-5 promoter-driven TGF-beta1(wt) transgenic (Tg) mice by bleomycin. The role of latent TGF-beta1 in pulmonary inflammation and fibrosis was examined at Days 7 and 28 after administration of bleomycin. Compared with littermate wild-type (WT) mice, TGF-beta1(wt) Tg mice had over twofold-higher levels of latent TGF-beta1 in both plasma and lung tissue, and were protected from bleomycin-induced pulmonary inflammation, such as up-regulation of IL-1beta, TNF-alpha, and macrophage chemotactic protein-1, and infiltration of CD3(+) T cells and F4/80(+) macrophages. In addition, the severity of lung fibrosis with massive collagen matrix accumulation was markedly reduced in TGF-beta1(wt) Tg mice. These protective effects were associated with higher levels of Smad7 and inactivation of both NF-kappaB and TGF-beta/Smad3 signaling pathways, in addition to an increase in forkhead box P3 (Foxp3)-dependent regulatory T cells, but inhibition of T helper 17-mediated lung injury. In summary, mice overexpressing latent TGF-beta1 are protected from bleomycin-induced lung injury. Triggering the Smad7 negative feedback mechanism to inhibit both NF-kappaB and TGF-beta/Smad signaling pathways, and enhancing the regulatory T cell response to counter-regulate T helper 17-mediated lung injury, are potential mechanisms by which latent TGF-beta1 protects against bleomycin-induced lung injury. |
