Other
11 Authors
- Xing Y,
- Li A,
- Krishnaveni MS,
- Banfalvi A,
- Minoo P,
- Li M,
- Lombardi V,
- Akbari O,
- Borok Z,
- Zhou B,
- Li C
| First Author | Li M | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 1 | Pages | 277-87 |
| PubMed ID | 21135509 | Mgi Jnum | J:171845 |
| Mgi Id | MGI:5000184 | Doi | 10.1172/JCI42090 |
| Citation | Li M, et al. (2011) Epithelium-specific deletion of TGF-beta receptor type II protects mice from bleomycin-induced pulmonary fibrosis. J Clin Invest 121(1):277-87 |
| abstractText | Idiopathic pulmonary fibrosis (IPF) is a chronic fibroproliferative pulmonary disorder for which there are currently no treatments. Although the etiology of IPF is unknown, dysregulated TGF-beta signaling has been implicated in its pathogenesis. Recent studies also suggest a central role for abnormal epithelial repair. In this study, we sought to elucidate the function of epithelial TGF-beta signaling via TGF-beta receptor II (TbetaRII) and its contribution to fibrosis by generating mice in which TbetaRII was specifically inactivated in mouse lung epithelium. These mice, which are referred to herein as TbetaRIINkx2.1-cre mice, were used to determine the impact of TbetaRII inactivation on (a) embryonic lung morphogenesis in vivo; and (b) the epithelial cell response to TGF-beta signaling in vitro and in a bleomycin-induced, TGF-beta-mediated mouse model of pulmonary fibrosis. Although postnatally viable with no discernible abnormalities in lung morphogenesis and epithelial cell differentiation, TbetaRIINkx2.1-cre mice developed emphysema, suggesting a requirement for epithelial TbetaRII in alveolar homeostasis. Absence of TbetaRII increased phosphorylation of Smad2 and decreased, but did not entirely block, phosphorylation of Smad3 in response to endogenous/physiologic TGF-beta. However, TbetaRIINkx2.1-cre mice exhibited increased survival and resistance to bleomycin-induced pulmonary fibrosis. To our knowledge, these findings are the first to demonstrate a specific role for TGF-beta signaling in the lung epithelium in the pathogenesis of pulmonary fibrosis. |
