The contributions of TGF-b signaling to cancer are complex but involve the inflammatory microenvironment as well as cancer cells themselves. In mice encoding a TGF-b mutant that precludes its binding to the latent TGF-b binding protein (Tgfb1 ), we observed multiorgan inflammation and an elevated incidence of various types of gastrointestinal solid tumors due to impaired conversion of latent to...

Myofibroblasts and TGF-b1 are implicated in Dupuytren’s contracture. Transforming growth factor b1(TGF-b1) (1–10 ng/ml) increases myofibroblast induction in Dupuytren’s fibroblasts and contraction in a collagen model. However, higher doses (20–30 ng/ml) inhibit contraction in dermal fibroblasts. We hypothesized higher doses of TGF-b1 would inhibit induction of myofibroblasts and contraction by ...

The mechanism(s) by which Smads mediate and modulate the transforming growth factor (TGF)-b signal transduction pathway in fibrogenesis are not well characterized. We previously showed that Smad3 promotes a2(I) collagen gene (COL1A2) activation in human glomerular mesangial cells, potentially contributing to glomerulosclerosis. Here, we report that Sp1 binding is necessary for TGF-b1-induced ty...

Heterogeneity of carcinoma-associated fibroblasts (CAF) has long been recognized, but the functional significance remains poorly understood. Here, we report the distinction of two CAF subtypes in oral squamous cell carcinoma (OSCC) that have differential tumor-promoting capability, one with a transcriptome and secretome closer to normal fibroblasts (CAF-N) and the other with a more divergent ex...

TGF-b1 is involved in many aspects of tissue development and homeostasis including hematopoiesis. The TAL1 transcription factor is also an important player of this latter process and is expressed very early in the myeloid and erythroid lineages. We previously established a link between TGF-b1 signaling and TAL1 by showing that the cytokine was able to induce its proteolytic degradation by the u...

Proliferation of fibrotic tissue (desmoplasia) is one of the hallmarks of several epithelial tumors including pancreatic adenocarcinoma. This tissue reaction may be deleterious or advantageous to the host or tumor. In a systematic analysis, we identified two growth factors expressed by human pancreatic carcinoma cells that are positively correlated with the ability to induce fibroblast prolifer...

insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-b1). This study tested the hypothesis that IGF-1 and TGF-b1 regulate immature cartilage compressive moduli and Poisson’s ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or followin...

Both the transforming growth factor b (TGF-b) and integrin signalling pathways have well-established roles in angiogenesis. However, how these pathways integrate to regulate angiogenesis is unknown. Here, we show that the extracellular matrix component, fibronectin, and its cellular receptor, a5b1 integrin, specifically increase TGF-b1and BMP-9-induced Smad1/5/8 phosphorylation via the TGF-b su...

Choi, Mary E. Cloning and characterization of a naturally occurring soluble form of TGF-b type I receptor. Am. J. Physiol. 276 (Renal Physiol. 45): F88–F95, 1999.—Transforming growth factor-b1 (TGF-b1) has been implicated to play an important role both in the process of normal development and in the pathogenesis of a wide variety of disease processes, including those of the kidney. TGF-b1 regul...

Yoo, Kee Hwan, Barbara A. Thornhill, and Robert L. Chevalier. Angiotensin stimulates TGF-b1 and clusterin in the hydronephrotic neonatal rat kidney. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R640–R645, 2000.—Unilateral ureteral obstruction (UUO) induces activation of the renin-angiotensin system and upregulation of transforming growth factor-b1 (TGF-b1; a cytokine modulating ce...