In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor b 1 (pCMV-TGFb 1) prevents the development of T helper cell type 1 (Th1)mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in...

Metastasis, the process whereby tumour cells disseminate and colonize distant organs, is the primary cause of cancer mortality. Diverse models have been proposed to explain how tumour cells acquire metastatic competency. Calon et al (2012) now provide insight into the molecular underpinnings of metastasis by describing a key stromal, non-cell autonomous role for Transforming Growth Factorbeta (...

Enhanced TGFb activity contributes to the accumulation of matrix proteins including collagen I (a2) by proximal tubular epithelial cells in progressive kidney disease. Although TGFb rapidly activates its canonical Smad signaling pathway, it also recruits noncanonical pathway involving mTOR kinase to regulate renal matrix expansion. The mechanism by which chronic TGFb treatment maintains increas...

Genetic analysis of TP63 implicates DNp63 isoforms in preservation of replicative capacity and cellular lifespan within adult stem cells. DNp63a is also an oncogene and survival factor that mediates therapeutic resistance in squamous carcinomas. These diverse activities are the result of genetic and functional interactions between TP63 and an array of morphogenic and morphostatic signals that g...

The assembly of the Smad complex is critical for TGFb signaling. Yet, the mechanisms that inactivate or empower nuclear Smad complexes are less understood. By means of siRNA screen we identified FAM (USP9x), a deubiquitinase (DUB) acting as essential and evolutionarily conserved component in TGFb and BMP signaling. Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits S...

Background Epithelial-mesenchymal transition (EMT) is a fundamental biologic process whereby epithelial cells detach from the surrounding tissue and acquire characteristics of mesenchymal cells, a unique motile, spindle-shaped cell with endto-end polarity. EMT can be induced or regulated by various growth and differentiation factors; among these, TGFb has received much attention as a major indu...

Background: The mechanism underlying the ability of fibroblasts to contract a collagen gel matrix is largely unknown. Fibroblasts from scarred (lesional) areas of patients with the fibrotic disease scleroderma show enhanced ability to contract collagen relative to healthy fibroblasts. Thrombospondin 1 (TSP1), an activator of latent transforming growth factor (TGF)b, is overexpressed by sclerode...

Although the regulation of epithelial morphogenesis is essential for the formation of tissues and organs in multicellular organisms, little is known about how signalling pathways control cell shape changes in space and time. In the Drosophila ovarian epithelium, the transition from a cuboidal to a squamous shape is accompanied by a wave of cell flattening and by the ordered remodelling of Ecadh...

Members of the transforming growth factor b (TGFb) superfamily of peptide growth factors regulate a broad range of cellular functions, including proliferation, apoptosis, extracellular matrix secretion and adhesion, terminal differentiation, and specification of developmental fate (Roberts and Sporn 1993; Wall and Hogan 1994; Moses and Serra 1996). Although regulation of each of these functions...

Colorectal cancer patients with high levels of tumorinfiltrating T cells have better survival than patients with low levels. It is not clear whether the T cells are directly responsible for improved prognosis or are a sign of a tumor that is more responsive to conventional cancer therapies. If tumor infiltrating T cell numbers are associated with improved outcome, then we hypothesize that incre...