XXXX kinase are required for transforming growth factor b induction of endothelial-mesenchymal transition in vitro.

@entity3113 @entity82 @entity17225 @entity19 @entity641 @entity12703 @entity2213 @entity22575 @entity31454 @entity669 @entity7112 @entity22416 @entity785
OBJECTIVE: The origin of the mesenchymal cells responsible for the intimal @entity82 in @entity785 ( @entity785 ) has not been fully identified. The present study was undertaken to investigate whether subendothelial mesenchymal cells may emerge through transdifferentiation of endothelial cells (ECs) into myofibroblasts via endothelial-mesenchymal transition (EndoMT) in vitro and to explore the signaling pathways involved in this process. METHODS: Primary @entity19 pulmonary ECs isolated by immunomagnetic methods with sequential anti- @entity22416 and anti- @entity31454 antibody selection were cultured in monolayers. Cell morphology and diacetylated low-density lipoprotein uptake assays confirmed their EC characteristics. The induction of EndoMT was assessed by determination of a-smooth muscle actin ( @entity3113 ), type I collagen, and @entity7112 expression, and the expression of the transcriptional repressor @entity22575 was analyzed. The signaling pathways involved were examined using small-molecule kinase inhibitors and RNA interference. RESULTS: @entity641 ( @entity641 ) induced @entity3113 and type I collagen expression and inhibited @entity7112 . These effects were mediated by a marked increase in @entity22575 expression and were abolished by treatment with either the @entity17225 @entity669 kinase inhibitor @entity2213 or the protein kinase C   (PKC  ) inhibitor @entity12703 . The inhibitory effects of @entity2213 and @entity12703 were mediated by inhibition of phosphorylation of glycogen synthase kinase 3b at residue Ser(9). These observations were confirmed in experiments using small interfering RNA specific for @entity17225 and PKC  . CONCLUSION: These results indicate that @entity17225 and PKC   are crucial for @entity641 -induced EndoMT and that @entity2213 and @entity12703 or similar kinase inhibitor molecules may be effective therapeutic agents for @entity785 and other fibroproliferative vasculopathies in which EndoMT plays a pathogenetic role.
