Heterogeneous response of nasal and lung fibroblasts to transforming growth factor-β1
Article first published online: 18 MAR 2008
© 2008 The Authors
Clinical & Experimental Allergy
Volume 38, Issue 5, pages 812–821, May 2008
How to Cite
Nonaka, M., Pawankar, R., Fukumoto, A. and Yagi, T. (2008), Heterogeneous response of nasal and lung fibroblasts to transforming growth factor-β1. Clinical & Experimental Allergy, 38: 812–821. doi: 10.1111/j.1365-2222.2008.02959.x
- Issue published online: 18 MAR 2008
- Article first published online: 18 MAR 2008
- Submitted 12 July 2006; revised 4 January 2008; accepted 15 January 2008
- pro-collagen type I;
- smooth muscle α-actin;
Background Nasal polyposis is characterized by marked oedema, sparse extracellular matrix (ECM) and proliferating blood vessels. Pulmonary fibrosis is characterized by inflammatory cells accumulation, considerable ECM deposition and vascular abnormalities. Although lung fibrosis is not only and necessarily an inflammatory disorder, we hypothesized that the difference between nasal polyposis and pulmonary fibrosis may, in part, be due to the heterogeneity between nasal and lung fibroblasts. Fibroblasts participate in the inflammatory response by releasing ECM proteins and cytokines. TGF-β is thought to participate in chronic inflammation and fibrosis. Myofibroblasts are the activated form of fibroblasts. A phenotypic hallmark of myofibroblasts is the expression of smooth muscle α-actin (SMA).
Objective We examined whether there is any heterogeneity between nasal and lung fibroblasts upon stimulation with TGF-β1 with regard to the synthesis of SMA, pro-collagen type I and vascular endothelial growth factor (VEGF) as well as translocation of Smad proteins.
Methods Fibroblasts lines were established from human biopsy tissue. The expression of SMA, pro-collagen type I, VEGF mRNA was evaluated by reverse transciptase RT-PCR. The amount of pro-collagen type I and VEGF was measured by ELISA. By immunocytochemistry, we analysed the expression of SMA and Smad2, 3, 4 in cultured fibroblasts.
Results TGF-β1 induced SMA and pro-collagen type I synthesis in lung, but not in nasal fibroblasts. By contrast, TGF-β1 induced VEGF synthesis in both lung and nasal fibroblasts. After stimulation with TGF-β1, Smad2, 3, 4 were translocated from the cytoplasm to the nucleus in lung fibroblasts, whereas only Smad3 was translocated in nasal fibroblasts.
Conclusion These results establish the heterogeneous responsiveness of fibroblast populations in the airways to TGF-β1 and that such a heterogeneity may contribute, at least in part, to the different pathological outcomes of inflammation in the upper and lower airways.