Increased expression of NAPDH oxidase 4 in XXXX dermal fibroblasts: regulation by transforming growth factor b.

@entity1 @entity5568 @entity82 @entity16228 @entity26 @entity7131 @entity1110 @entity2533 @entity14877 @entity785
OBJECTIVE: @entity785 ( @entity785 ) is characterized by severe and often progressive @entity82 of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive @entity26 species (ROS)-mediated oxidative stress has been implicated. @entity16228 is 1 of 7 isoforms of @entity1110 oxidase responsible for the generation of ROS. The purpose of this study was to examine @entity16228 expression in skin and cultured dermal fibroblasts from @entity785 @entity1 and to examine its regulation by @entity2533 ( @entity2533 ). METHODS: @entity16228 was assessed in normal and @entity785 skin by immunohistologic analysis and in normal and @entity785 cultured dermal fibroblasts by quantitative polymerase chain reaction analysis, fluorescence microscopy, and Western blotting. ROS levels were assessed by fluorescence measurement of @entity5568 production. Specific kinase inhibitors were used to study the @entity2533 signaling involved in @entity16228 stimulation. @entity16228 inhibition/down-regulation was induced with a selective @entity16228 small-molecule inhibitor and @entity16228 small interfering RNA (siRNA). RESULTS: In contrast with normal skin fibroblasts, those from @entity785 skin showed intense @entity16228 staining. Cultured @entity785 fibroblasts displayed increased @entity16228 expression. @entity2533 caused potent @entity16228 protein and messenger RNA stimulation in normal and @entity785 fibroblasts, which was mediated by the @entity7131   ( @entity7131  ) and @entity14877 pathways. @entity16228 knockdown in @entity785 fibroblasts reduced the production of ROS and lowered the expression of type I collagen. CONCLUSION: @entity16228 expression and production were found to be constitutively elevated in @entity785 skin and cultured @entity785 dermal fibroblasts. @entity2533 stimulated @entity16228 expression in normal and @entity785 fibroblasts through @entity7131   and @entity14877 signaling pathways. A small-molecule @entity16228 inhibitor decreased collagen and fibronectin production by normal and @entity785 fibroblasts, and @entity16228 siRNA knockdown reduced ROS and collagen production by @entity785 fibroblasts. These results demonstrate the involvement of @entity16228 in @entity785 -associated @entity82 and indicate @entity16228 inhibitors as novel therapeutic approaches for @entity785 .
