%0 Journal Article %A Michael Schuliga %A Trudi Harris %A Yuxiu Xia %A Zhexing Wang %A Xuehua Zhang %A Peter Lee %A Alastair Stewart %T FGF-2 modulates human airway smooth muscle contractile protein expression and cell stiffness %D 2013 %J European Respiratory Journal %P P566 %V 42 %N Suppl 57 %X In asthma, fibroblast growth factor-2 (FGF-2) has an important (patho)physiological role. We have investigated the effect of FGF-2 on airway smooth muscle (ASM) differentiation in vitro by measuring increases in contractile protein expression and cell stiffness. Differentiation of human ASM cells was assessed following incubation with TGF-β (100pM) for 48h, in the absence or presence of FGF-2 (300pM) and the TGF-β-R kinase (Alk-5) inhibitor, SB431542 (10μM). Differentiation was measured by changes in levels of mRNA of the contractile proteins, SM22 and calponin, using real time PCR. Changes in cell stiffness were assessed by micropipette aspiration. FGF-2 inhibited TGF-β-stimulated increases in SM22 and calponin gene expression (n=15, P<0.01), in a MAPK (ERK1/2) signal transduction-dependent manner. Furthermore, FGF-2 attenuated TGF-β-stimulated increases in ASM cell stiffness (n=4-5, P<0.01). The effects of FGF-2 on contractile expression are independent of smad signaling as TGF-β-stimulated increases in smad 2/3-phosphorylation were not attenuated by FGF-2. Furthermore, TGF-β-stimulated production of interleukin-6, which is dependent on smad 2/3 signaling, was not influenced by FGF-2 (n=4, P>0.05). The addition of FGF-2 24h after TGF-β still reduced contractile protein expression, even when the TGF-β-receptor kinase inhibitor, SB431542 (10μM), was added 1h before FGF-2. These data suggests that FGF-2 is able to reduce contractile protein gene expression in ASM cells in a manner that occurs independently of concurrent TGF-β-signaling. A better understanding the mechanism of action of FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma. %U https://erj.ersjournals.com/content/erj/42/Suppl_57/P566.full.pdf