367회 TGF-β/Smad signaling as potential therapeutic targets in human di…

367회

연사 :  박 석 희, 인하대학교 의과대학 병리학교실

제목:  TGF-β/Smad signaling as potential therapeutic targets in human diseases

Abstract

Transforming Growth Factor-β (TGF-β) is a multifunctional cytokine, capable of regulating the growth, differentiation and apoptosis of virtually all cell types. A prominent signaling pathway is mediated by a set of novel proteins called Smads, which participate in a direct signaling pathway involving their phosphorylation by the type 1 receptor kinase and subsequent translocation to the nucleus to play functional roles in transcriptional complexes. TGF-β has been implicated in numerous disease states including immune-mediated diseases, fibrotic diseases, angiogenic diseases and cancer. We here discuss our ongoing projects to understand the possibilities of TGF-β/Smad signaling as therapeutic targets. First, we demonstrate how co-treatment of low-dose Staurosporine (STS) and TGF-β1, which alone has little effect on cell death, induces apoptosis in MvlLu mink lung epithelial cells, but not its clonal variant R1B cells lacking functional TGF-β signaling. In addition, we show that this co-treatment further enhances TGF-β signaling and alters MAPK activity through decreasing phosphor-ERK as a pro-survival signal. Second, we reveal the results that Smad6, one of the inhibitory Smads in TGF-β/Smad signaling, has novel function during anti-inflammation process. Smad6 negatively regulates Interleukin-1 Receptor (IL-1R)/Toll-like Receptor (TLR) signaling through interactions with Pellino-1 protein, which was identified by yeast two-hybrid system by using Smad6. These results are the first report suggesting cross-talk between IL-1R/TLR signaling and TGF-β signaling. Based on the results in each project, the possibility of TGF-beta/Smad signaling as therapeutic targets will be discussed.