| First Author | Li G | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 11 | Pages | 5359-70 |
| PubMed ID | 24127553 | Mgi Jnum | J:207032 |
| Mgi Id | MGI:5554323 | Doi | 10.4049/jimmunol.1301596 |
| Citation | Li G, et al. (2013) Lyn mitigates mouse airway remodeling by downregulating the TGF-beta3 isoform in house dust mite models. J Immunol 191(11):5359-70 |
| abstractText | Chronic airway remodeling is a serious consequence of asthma, which is caused by complex but largely unknown mechanisms. Despite versatile functions, the role of Lyn in chronic airway remodeling remains undefined. Using Lyn(-/-) mice, we show that continual exposure (for 8 wk) of house dust mite extracts induced a severe phenotype of chronic airway remodeling, including exacerbated mucus production, collagen deposition, dysregulated cytokine secretion, and elevated inflammation. Strikingly, a significant increase in TGF-beta3 rather than TGF-beta1 was observed in Lyn(-/-) mouse lungs compared with lungs in wild-type mice. Furthermore, TGF-beta3 neutralizing Abs not only inhibited the expression of STAT6 and Smad2/3 but also decreased phosphorylation of Smad2 and NF-kappaB in Lyn(-/-) mouse lungs. In addition, both recombinant and adenoviral TGF-beta3 significantly promoted epithelial-to-mesenchymal transition and intensified collagen I production and MUC5AC expression. Further examination of chronic asthma patients showed that a decreased Lyn correlated with the severity of airway inflammation and mucus hypersecretion. Finally, Lyn may critically regulate airway remodeling by directly interacting with TGF-beta3. Collectively, these findings revealed that Lyn regulates TGF-beta3 isoform and modulates the development of airway remodeling, which may have therapeutic implications for severe chronic asthma. |
