The effects of knockdown of XXXX on gene expression and function in cultured @entity1 arterial smooth muscle cells.

@entity1 @entity650 @entity1356 @entity10688 @entity9067
Rho-associated kinase (ROCK) and @entity10688 ( @entity10688 ) have been implicated in diverse physiological functions. @entity9067 phosphorylates and activates @entity10688 suggesting that at least some of these physiological functions may require both enzymes. To test the hypothesis that sequential activation of @entity9067 and @entity10688 is commonly involved in regulatory pathways, we utilized siRNA to knock down @entity9067 and @entity10688 in cultured @entity1 arterial smooth muscle cells (SMC). Microarray analysis using a whole-transcript expression chip identified changes in gene expression induced by @entity9067 and @entity10688 knockdown. @entity9067 knockdown affected the expression of 553 genes, while @entity10688 knockdown affected the expression of 390 genes. A high incidence of regulation of transcription regulator genes was observed in both knockdowns. Other affected groups included transporters, kinases, peptidases, transmembrane and G protein-coupled receptors, growth factors, phosphatases and ion channels. Only 76 differentially expressed genes were common to @entity9067 and @entity10688 knockdown. Ingenuity Pathway Analysis identified five pathways shared between the two knockdowns. We focused on cytokine signaling pathways since @entity9067 knockdown up-regulated 5 and down-regulated 4 cytokine genes, in contrast to @entity10688 knockdown, which affected the expression of only two cytokine genes (both down-regulated). @entity650 gene expression and secretion of @entity650 protein were up-regulated by @entity9067 knockdown, whereas @entity10688 knockdown reduced @entity650 mRNA expression and @entity650 protein secretion and increased @entity9067 protein expression, suggesting that @entity9067 may inhibit @entity650 secretion. @entity1356 mRNA and protein levels were increased in response to @entity9067 knockdown. Differences in the effects of @entity9067 and @entity10688 knockdown on cell cycle regulatory genes suggested that @entity9067 and @entity10688 regulate the cell cycle by different mechanisms. @entity9067 , but not @entity10688 knockdown reduced the viability and inhibited proliferation of vascular SMC. We conclude that @entity9067 and @entity10688 have diverse, but predominantly distinct regulatory functions in vascular SMC and that @entity9067 -mediated activation of @entity10688 is not involved in most of these functions.
