Mutations in the gene for the latent transforming growth factor beta binding protein 4 (LTBP4) cause autosomal recessive cutis laxa type 1C. To understand the molecular disease mechanisms of this disease, we investigated the impact of LTBP4 loss on transforming growth factor beta (TGFβ) signaling. Despite elevated extracellular TGFβ activity, downstream signaling molecules of the TGFβ pathway, ...

RATIONALE Wound healing after myocardial infarction involves a highly regulated inflammatory response that is initiated by the appearance of neutrophils to clear out dead cells and matrix debris. Neutrophil infiltration is controlled by multiple secreted factors, including the master regulator transforming growth factor β (TGFβ). Broad inhibition of TGFβ early postinfarction has worsened post-m...

To improve cartilage formation by bone marrow-derived mesenchymal stem cells (BMSCs), the signaling mechanism governing chondrogenic differentiation requires better understanding. We previously showed that the transforming growth factor-β (TGFβ) receptor ALK5 is crucial for chondrogenesis induced by TGFβ. ALK5 phosphorylates SMAD2 and SMAD3 proteins, which then form complexes with SMAD4 to regu...

Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) expression in acute promyelocytic leukemia (APL) impairs transforming growth factor beta (TGFβ) signaling, leading to cell growth advantage. Halofuginone (HF), a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice subjec...

Transforming growth factor β (TGFβ) causes the acquisition of epithelial-mesenchymal transition (EMT). Although the tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) can negatively regulate many signaling pathways activated by TGFβ, hyperactivation of these signaling pathways is observed in lung cancer cells. We recently showed that PTEN might be subject t...

Enhanced TGFβ activity contributes to the accumulation of matrix proteins including collagen I (α2) by proximal tubular epithelial cells in progressive kidney disease. Although TGFβ 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 TGFβ treatment maintains increas...

BACKGROUND This study investigates the effects of human bone marrow-derived mesenchymal stem cell (hMSC) on migration and proliferation ability of hepatocellular carcinoma (HCC) with high- and low-metastatic potential. METHODS The hMSC and transforming growth factor-β1 (TGFβ-1) gene infected hMSC were co-cultured with hepatoma cells. The ability of cells migration was assessed by Transwell as...

airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard  lung patients. mustard lung is the  general description  for  the  chronic obstructive  pulmonary  disease induced  by  sulfur  mustard(sm). pulmonary  disease was diagnosed as the most important  disorder in individuals that had been exposed to sulfur mustard. sulfur mustard is a chemical w...

Transforming growth factor-β (TGFβ) is a cytokine with autocrine and paracrine action in the testis and potent immunoregulatory and anti-inflammatory activities. In the present study, we examined the concentration of latent (acid-activatable) and free (active) TGFβ in seminal plasma from normal subjects (n J 23) and infertile (n J 40) patients, by using a TGFβ specific immunoenzymological assay...

Transforming growth factor β1 (TGF-β1) increases dehydro-epiandrosterone (DHEA) metabolism to androgens and prostate-specific antigen (PSA) in a prostate tissue model where stromal (6S) cells and epithelial (LAPC-4) cells are cocultured. Red clover (RC) isoflavones inhibits transforming growth factor (TGF)-β-induced androgenicity. Mechanisms controlling those activities were explored. Three hyd...