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Transforming growth factor-?-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2.


ABSTRACT: In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-? (TGF-?)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of human ASM cells after incubation with TGF-? (100 pM) and/or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and collagen remodeling. FGF-2 inhibited TGF-?-stimulated increases in transgelin (SM22) and calponin gene expression (n = 15, P < 0.01) in an extracellular signal-regulated kinase 1/2 (ERK1/2) signal transduction-dependent manner. The abundance of ordered ?-smooth muscle actin (?-SMA) filaments formed in the presence of TGF-? were also reduced by FGF-2, as was the ratio of F-actin to G-actin (n = 8, P < 0.01). Furthermore, FGF-2 attenuated TGF-?-stimulated increases in ASM cell stiffness and the ASM-mediated contraction of lattices, composed of collagen fibrils (n = 5, P < 0.01). However, the TGF-?-stimulated production of IL-6 was not influenced by FGF-2 (n = 4, P > 0.05), suggesting that FGF-2 antagonism is selective for the regulation of ASM cell contractile protein expression, organization, and function. Another mitogen, thrombin (0.3 U ml(-1)), exerted no effect on TGF-?-regulated contractile protein expression (n = 8, P > 0.05), ?-SMA organization, or the ratio of F-actin to G-actin (n = 4, P > 0.05), suggesting that the inhibitory effect of FGF-2 is dissociated from its mitogenic actions. The addition of FGF-2, 24 hours after TGF-? treatment, still reduced contractile protein expression, even when the TGF-?-receptor kinase inhibitor, SB431542 (10 ?M), was added 1 hour before FGF-2. We conclude that the ASM cell differentiation promoted by TGF-? is antagonized by FGF-2. A better understanding of the mechanism of action for FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma.

SUBMITTER: Schuliga M 

PROVIDER: S-EPMC3604085 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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Transforming growth factor-β-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2.

Schuliga Michael M   Javeed Aqeel A   Harris Trudi T   Xia Yuxiu Y   Qin Chengxue C   Wang Zhexing Z   Zhang Xuehua X   Lee Peter V S PV   Camoretti-Mercado Blanca B   Stewart Alastair G AG  

American journal of respiratory cell and molecular biology 20121213 3


In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-β (TGF-β)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of human ASM cells after incubation with TGF-β (100 pM) and/or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and col  ...[more]

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