1 BAMBI acts as a pseudoreceptor for the TGFβ type I receptor family and negative modulator of TGFβ kinase 2 signaling and BAMBI-/-mice show mild endothelial dysfunction. As diabetic glomerular disease is associated 3 with TGFβ overexpression and microvascular alterations, we examined the effect of diabetes on glomerular 4 BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with ...

Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT) during embryogenesis and in tumors. The effect of TGFβ, on ΕΜΤ, is conveyed by induction of the pro-invasive transcription factor Snail1. In this study, we report that TGFβ stimulates Snail1 sumoylation in aggressive prostate, breast and lung cancer cells. Sumoylation of Snail1 lysine residue 23...

Signal transduction by the Smad pathway elicits critical biological responses to many extracellular polypeptide factors, including TGFβ and bone morphogenetic protein. Regulation of Smad signaling imparts several cytoplasmic and nuclear mechanisms, some of which entail protein phosphorylation. Previous work established a protein complex between Smad4 and the scaffolding protein LKB1-interacting...

Introduction: Primary Cicatricial Alopecia (PCA) is an autoimmune condition that affects the skin and causes hair loss in patients. In PCA follicles of patients are irreversibly damaged replaced with fibrous tissue. This diseased lends relevance to our work since fibrosis raises potential may be affected some way by Epithelial Mesenchymal Transition (EMT). We used small interfering RNAs (siRNA)...

Tissue inhibitor of metalloproteinase 1 (TIMP1) controls matrix metalloproteinase activity through 1:1 stoichiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol (GPI) anchor (TIMP-1 GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1 GPI treated renal cell carcinoma cells show increased apoptosis and reduced proliferation. Transcriptom...

Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFβ pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFβ-responsive genes. In vivo ...

Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer. A number of signaling pathways like PI3K, Rho and TGFβ/SMAD drive the invasive nature of HNSCC. The PI3K pathway is the most altered pathway in HNSCC. Both upstream and downstream members of this pathway have been found to be mutated or overexpressed leading to an increase in cell invasion. The Rho pathway is also common...

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Despite recent advances in the development of targeted therapies, patients with advanced disease remain incurable, mostly because metastatic non-small cell lung carcinomas (NSCLC) eventually become resistant to tyrosine kinase inhibitors (TKIs). Kinase inhibitors have the potential for target promiscuit...

OBJECTIVE To investigate transforming growth factor β (TGFβ) regulation of CCN3 expression in cells of the nucleus pulposus. METHODS Real-time reverse transcription-polymerase chain reaction and Western blot analyses were used to measure CCN3 expression in the nucleus pulposus. Transfections were used to measure the effect of Smad3, MAPKs, and activator protein 1 (AP-1) on TGFβ-mediated CCN3 ...

Signalling by TGFβ superfamily factors plays an important role in tissue growth and cell proliferation. In Drosophila, the activity of the TGFβ/Activin signalling branch has been linked to the regulation of cell growth and proliferation, but the cellular and molecular basis for these functions are not fully understood. In this study, we show that both the RII receptor Punt (Put) and the R-Smad ...