PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation.

摘要: P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects inflammation on PAK1 signaling its role in colitis-driven carcinogenesis. p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, Western blot. C57BL6/J wildtype mice treated a single intraperitoneal TNFα injection. Small intestinal organoids from these PAK1-KO cultured TNFα. NF-κB PPARγ analyzed upon overexpression silencing for transcriptional/translational regulation. expression activation was increased luminal epithelial surface inflammatory bowel disease colitis-associated cancer. phosphorylated treatment IFNγ, IL-1β, In vivo, administered showed villi, which associated nuclear p65 activation. translocation downstream strongly inhibited small organoids. induced PAK1–p65 interaction as visualized co-immunoprecipitation, translocation, transactivation, all impeded kinase-dead PAK1. Moreover, downregulated mesalamine recovered through inhibition. On other hand NF-κB, using BADGE, antagonist. Altogether data demonstrate that cancer promote activity via suppression cells.