FIBROSIS IN VITAL ORGANS causes significant morbidity and mortality worldwide. Although our understanding of the cellular and molecular mechanisms underlying fibrosis has grown tremendously over the last decades, effective treatments that halt, reverse, or prevent the pathological accumulation and remodeling of extracellular matrix (ECM) are lacking. Recent advances revealed that ECM stiffening...

CAVEOLAE ARE SMALL, invaginated surface structures in the plasma membrane of fully differentiated cells such as endothelial cells, epithelial cells, adipocytes, and fibroblasts. The principal components of caveolae are proteins called caveolins, of which caveolin-1 (cav-1) is best characterized. The expression of cav-1 decrease in transformed cells, implying that cav-1 is an important molecule ...

Cardiac fibrosis is characterized by net accumulation of extracellular matrix in the myocardium and is an integral component of most cardiac pathological conditions. Fibrotic remodeling of the ventricle has profound consequences on cardiac function. Increased deposition of interstitial collagen in the perimysial space is initially associated with a stiffer ventricle and diastolic dysfunction. A...

Background: Premature birth and respiratory distress syndrome (RDS) are risk factors for disturbed lung development and bronchopulmonary dysplasia (BPD). The molecular mechanisms related to prematurity and BPD remain largely unknown. Epithelial expression of the transcription factor GATA-6 has been implicated in normal and abnormal murine lung development. Objectives: The possible involvement o...

Transforming growth factor (TGF) 1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF31 and/or loss of TGF-f 1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human ca...

Small molecule inhibitors have proven extremely useful for investigating signal transduction pathways and have the potential for development into therapeutics for inhibiting signal transduction pathways whose activities contribute to human diseases. Transforming growth factor (TGF) is a member of a large family of pleiotropic cytokines that are involved in many biological processes, including g...

We studied the effect of tumor necrosis factor a (TNF-a) on transforming growth factor 3 (TGF) secretion by human breast cell lines to further characterize the antitumor effects of TNF-a. We found that TNF-a increased the secretion of TGFin two established breast cancer cell lines (MCF-7 and ZR-75-1) but not in two immortalized human mammary epithelial cell lines (184B5 and MCF1OA). In MCF-7 ce...

The purpose of this study was to determine whether production of liver metastasis by human colon carcinoma (HCC) cells depends on the response of tumor cells to organderived growth factors. HCC cells were isolated from several surgical specimens whose malignant potential differed (Dukes’ stage B or D tumors), adapted to grow in culture, and assessed for expression of the epidermal growth factor...

and Introduction Abstract Statins, HMG-CoA reductase inhibitors, are common cholesterol-lowering drugs. Recent studies suggest that statins may have potential as novel treatments for diverse conditions, ranging from sepsis and inflammatory diseases to chronic wounds and bone fractures. The diverse pleiotropic actions of statins are probably related to reduced isoprenylation of downstream target...

Transforming growth factor(TGF ) is a major mediator of normal wound healing and of pathological conditions involving fibrosis, such as idiopathic pulmonary fibrosis. TGF also stimulates the differentiation of myofibroblasts, a hallmark of fibrotic diseases. In this study, we examined the underlying processes of TGF RI kinase activity in myofibroblast conversion of human lung fibroblasts using ...