Functional characterization of serum- and growth factor-induced phenotypic changes in intact XXXX tracheal smooth muscle.

@entity4357 @entity2306 @entity665 @entity16033 @entity3960 @entity4286 @entity2710 @entity291 @entity4338
1. The present study aims to investigate whether phenotypic changes, reported to occur in cultured isolated @entity3960 ( @entity3960 ) cells, are of relevance to intact @entity3960 . Moreover, we aimed to gain insight into the signalling pathways involved. 2. Culturing of @entity291 tracheal smooth muscle (BTSM) strips for up to 8 days in the presence of 10% foetal bovine serum caused a time-dependent (t(1/2)=2.8 days) decrease in maximal contraction (E(max)) to @entity2710 compared to serum-deprived controls (E(max)=74+/-4% at day 8). A reduced E(max) was also found using @entity16033 (30 ng ml(-1)) and platelet-derived growth factor (30 ng ml(-1)), but not using epidermal growth factor (10 ng ml(-1)) (E(max)=83+/-3, 67+/-8, 100+/-4%, respectively). Similar serum and growth factor-induced changes in E(max) were found for @entity4338 -induced contraction (65+/-9, 80+/-7, 64+/-11% and 107+/-2%, respectively). 3. Strong correlations were found between the growth factor-induced reductions in E(max) and their proliferative responses, assessed by @entity665 -incorporation, in BTSM cells. (r=0.97, P=0.002 for @entity2710 and r=0.93, P=0.007 for @entity4338 ). 4. The PDGF-induced reduction in E(max) was inhibited completely by combined treatment with either @entity4286 (30 micro M) or @entity2306 (10 micro M). 5. These results indicate that serum and growth factors may cause a functional shift towards a less contractile phenotype in intact BTSM, which is associated with their proliferative response and dependent on signalling pathways involving the mitogen-activated protein kinase pathway and the @entity4357 -3-kinase pathway.
