Abstract
Little is understood of the molecular mechanisms by which fibrotic diseases such as in Scleroderma, are manifested by interleukins (IL) 4 and 13. Studies support a role for the JNK signaling pathway via transcription factors c-Jun and ATF2, being involved in activating the collagen promoter and translation of the collagen gene. To examine the role of JNK signaling in IL-4/IL-13-induced collagen gene activation, we transfected human fibroblasts with a luciferase reporter plasmid under control of the α2(I) collagen promoter to assess JNK signaling on type I collagen promoter activity. We reveal a critical role for JNK 1 in IL-4/IL-13-induced collagen promoter activity subsequent to ectopic expression of c-Jun and ATF2. In contrast, introduction of a dominant negative (dn) mutant reduces basal and cytokine-induced promoter activity. We demonstrate that the JNK signaling pathway leading to the activation of the collagen gene in fibroblasts is effective not only for TGF-β signaling but also for IL-4/IL-13 signaling.
