Transforming growth factor-β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the ki...

BMP, activin, membrane-bound inhibitor (BAMBI) acts as a pseudo-receptor for the transforming growth factor (TGF)-β type I receptor family and a negative modulator of TGF-β kinase signaling, and BAMBI(-/-) mice show mild endothelial dysfunction. Because diabetic glomerular disease is associated with TGF-β overexpression and microvascular alterations, we examined the effect of diabetes on glomer...

Fibrosis leads to failure of the skin, lungs, and other organs in systemic sclerosis (SSc); accounts for substantial morbidity mortality; lacks effective therapy. Recent findings implicated TGFβ-activated kinase 1 (TAK1), triggered by TGF-β toll-like receptor signaling, SSc pathogenesis. The objectives were evaluate activation TAK1 signaling axis patients antifibrotic ability pharmacological bl...

Transforming growth factor-β (TGF-β) signaling plays a key role in progression and metastasis of HCC. This study was undertaken to gain the proof of concept of a small-molecule inhibitor of TGF-β type I receptor kinase, EW-7197 as a potent anti-cancer therapy for HCC. We identified tissue inhibitors of metalloproteinases-1 (TIMP-1) as one of the secreted proteins of hepatic stellate cells (HSCs...

Areca nut (AN) chewing is associated with chronic kidney disease (CKD). However, the molecular mechanisms of AN-induced CKD are not known. Thus, we studied the effects of arecoline, a major alkaloid of AN, on proximal tubule (LLC-PK1) cells in terms of cytotoxicity, fibrosis, transforming growth factor-β (TGF-β) and c-Jun N-terminal kinase (JNK). We found that arecoline dose (0.1-0.5mM) and tim...

Transforming growth factor-β (TGF-β) is a potent growth inhibitor in normal epithelial cells. However, a number of malignant tumors produce excessive amounts of TGF-β, which affects the tumor-associated microenvironment by furthering the progression of tumorigenicity. Although it is known that the tumor-associated microenvironment often becomes hypoxic, how hypoxia influences TGF-β signaling in...

Previous studies have demonstrated that an increase in dietary NaCl (salt) intake stimulated endothelial cells to produce transforming growth factor-β (TGF-β). The intent of the present study was to determine the functional significance of increased TGF-β on endothelial cell function. Young Sprague-Dawley rats were fed diets containing 0.3 or 8.0% NaCl for 2 days before treatment with a specifi...

Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. ...

Multiple transforming growth factor (TGF)-β-induced fibrogenic signals have been described in vitro. To evaluate mechanisms in vivo, we used an adriamycin nephropathy model in 129x1/Svj mice that display massive proteinuria by days 5 to 7 and pathological findings similar to human focal segmental glomerulosclerosis by day 14. TGF-β mRNA expression increased after day 7 along with nuclear transl...

objective(s):fuzheng huayu recipe (fzhy) exerts significant protective effects against liver fibrosis by strengthening the body’s resistance and removing blood stasis. however, the molecular mechanisms through which fzhy affects liver fibrosis are still unclear. in this study, we examined the expression levels of factors involved in the inhibitor κb kinase-β (ikk-β)/nuclear factor-κb (nf-κb) an...