| First Author | Walters DM | Year | 2005 |
| Journal | Am J Pathol | Volume | 167 |
| Issue | 5 | Pages | 1221-9 |
| PubMed ID | 16251407 | Mgi Jnum | J:102403 |
| Mgi Id | MGI:3607464 | Doi | 10.1016/S0002-9440(10)61210-2 |
| Citation | Walters DM, et al. (2005) Susceptibility of signal transducer and activator of transcription-1-deficient mice to pulmonary fibrogenesis. Am J Pathol 167(5):1221-9 |
| abstractText | The signal transducer and activator of transcription (Stat)-1 mediates growth arrest and apoptosis. We postulated that lung fibrosis characterized by excessive proliferation of lung fibroblasts would be enhanced in Stat1-deficient (Stat1(-/-)) mice. Two weeks after bleomycin aspiration (3 U/kg), Stat1(-/-) mice exhibited a more severe fibroproliferative response and significantly elevated total lung collagen compared to wild-type mice. Growth factors [epidermal growth factor (EGF) or platelet-derived growth factor (PDGF)] enhanced [(3)H]thymidine uptake in lung fibroblasts isolated from Stat1(-/-) mice compared to wild-type mice. Interferon (IFN)-gamma, which signals growth arrest via Stat1, inhibited EGF- or PDGF-stimulated mitogenesis in wild-type fibroblasts but enhanced [(3)H]thymidine uptake in Stat1(-/-) fibroblasts. Moreover, IFN-gamma treatment in the absence of growth factors induced a concentration-dependent increase in [(3)H]thymidine uptake in Stat1(-/-) but not wild-type fibroblasts. Mitogen-activated protein kinase (ERK-1/2) phosphorylation in response to PDGF or EGF did not differ among Stat1(-/-) and wild-type fibroblasts. However, Stat3 phosphorylation induced by PDGF, EGF, or IFN-gamma increased twofold in Stat1(-/-) fibroblasts compared to wild-type fibroblasts. Our findings indicate that Stat1(-/-) mice are more susceptible to bleomycin-induced lung fibrosis than wild-type mice due to 1) enhanced fibroblast proliferation in response to growth factors (EGF and PDGF), 2) stimulation of fibroblast growth by a Stat1-independent IFN-gamma signaling pathway, and 3) increased activation of Stat3. |
