BACKGROUND AND OBJECTIVE: Airway smooth muscle (ASM) cell hyperplasia is a key feature of airway remodelling. Mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) are key components in signal transduction associated with cell proliferation; MAPK consists of the extracellular signal-regulated kinase (ERK), p38MAPK and c-Jun NH(2)-terminal kinase (JNK). The effect of transforming growth factor (TGF)-beta on the proliferation of ASM cells, the release of vascular endothelial growth factor (VEGF) by ASM cells and relevant signal transduction pathways were investigated. METHODS: ASM cells were growth-arrested for 48 h then stimulated with platelet-derived growth factor (PDGF), TGF-beta and dexamethasone. ASM cells were also treated with specific inhibitors of MAPK (PD98059), PI3K (wortmannin) and JNK (SP600125). Cell proliferation and VEGF concentrations were measured. RESULTS: TGF-beta neither augmented ASM cell proliferation nor showed a synergistic effect on PDGF-mediated ASM cell proliferation. Dexamethasone did not suppress ASM cell proliferation. VEGF release was augmented by TGF-beta stimulation in a time-dependent manner, and was further enhanced by co-stimulation with PDGF and TGF-beta. Dexamethasone suppressed VEGF release significantly. TGF-beta enhanced PI3K phosphorylation, while PDGF augmented both ERK and PI3K phosphorylation. Wortmannin inhibited both TGF-beta- and PDGF-stimulated VEGF release. CONCLUSIONS: TGF-beta may facilitate airway remodelling by promoting VEGF release through the PI3K pathway, rather than via ASM cell proliferation.
BACKGROUND AND OBJECTIVE: Airway smooth muscle (ASM) cell hyperplasia is a key feature of airway remodelling. Mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) are key components in signal transduction associated with cell proliferation; MAPK consists of the extracellular signal-regulated kinase (ERK), p38MAPK and c-Jun NH(2)-terminal kinase (JNK). The effect of transforming growth factor (TGF)-beta on the proliferation of ASM cells, the release of vascular endothelial growth factor (VEGF) by ASM cells and relevant signal transduction pathways were investigated. METHODS: ASM cells were growth-arrested for 48 h then stimulated with platelet-derived growth factor (PDGF), TGF-beta and dexamethasone. ASM cells were also treated with specific inhibitors of MAPK (PD98059), PI3K (wortmannin) and JNK (SP600125). Cell proliferation and VEGF concentrations were measured. RESULTS:TGF-beta neither augmented ASM cell proliferation nor showed a synergistic effect on PDGF-mediated ASM cell proliferation. Dexamethasone did not suppress ASM cell proliferation. VEGF release was augmented by TGF-beta stimulation in a time-dependent manner, and was further enhanced by co-stimulation with PDGF and TGF-beta. Dexamethasone suppressed VEGF release significantly. TGF-beta enhanced PI3K phosphorylation, while PDGF augmented both ERK and PI3K phosphorylation. Wortmannin inhibited both TGF-beta- and PDGF-stimulated VEGF release. CONCLUSIONS:TGF-beta may facilitate airway remodelling by promoting VEGF release through the PI3K pathway, rather than via ASM cell proliferation.
Authors: Charalambos Michaeloudes; Po-Jui Chang; Mario Petrou; Kian Fan Chung Journal: Am J Respir Crit Care Med Date: 2011-10-15 Impact factor: 21.405
Authors: Daniel R Principe; Jennifer A Doll; Jessica Bauer; Barbara Jung; Hidayatullah G Munshi; Laurent Bartholin; Boris Pasche; Chung Lee; Paul J Grippo Journal: J Natl Cancer Inst Date: 2014-02 Impact factor: 13.506
Authors: Charalambos Michaeloudes; Maria B Sukkar; Nadia M Khorasani; Pankaj K Bhavsar; Kian Fan Chung Journal: Am J Physiol Lung Cell Mol Physiol Date: 2010-12-03 Impact factor: 5.464