Chronic exposure to perfluorinated compounds: Impact on airway hyperresponsiveness and inflammation.

Emerging epidemiological evidence reveals a link between lung disease and exposure to indoor pollutants such as perfluorinated compounds (PFCs). PFC exposure during critical developmental stages may increase asthma susceptibility. Thus, in a murine model, we tested the hypothesis that early life and continued exposure to two ubiquitous household PFCs, perfluorooctanoic acid (PFOA) and perflurooctanesulfonic acid (PFOS), can induce lung dysfunction that exacerbates allergen-induced airway hyperresponsiveness (AHR) and inflammation.

FGF-16 is a target for adrenergic stimulation through NF-kappaB activation in postnatal cardiac cells and adult mouse heart.

Aims: The fibroblast growth factor (FGF) family plays an important role in cardiac growth and development. However, only FGF-16 RNA levels are reported to increase during the perinatal period and to be expressed preferentially in the myocardium, suggesting control at the transcriptional level and a role for FGF-16 in the postnatal heart. Beyond the identification of two TATA-like elements (TATA1 and TATA2) in the mouse FGF-16 promoter region and the preferential cardiac activity of TATA2, there is no report of Fgf-16 gene regulation.

FGF-16 is required for embryonic heart development.

Fibroblast growth factor 16 (FGF-16) expression has previously been detected in mouse heart at mid-gestation in the endocardium and epicardium, suggesting a role in embryonic heart development. More specifically, exogenously applied FGF-16 has been shown to stimulate growth of embryonic myocardial cells in tissue explants. We have generated mice lacking FGF-16 by targeting the Fgf16 locus on the X chromosome.

FGF-16 is released from neonatal cardiac myocytes and alters growth-related signaling: a possible role in postnatal development.

FGF-16 has been reported to be preferentially expressed in the adult rat heart. We have investigated the expression of FGF-16 in the perinatal and postnatal heart and its functional significance in neonatal rat cardiac myocytes. FGF-16 mRNA accumulation was observed by quantitative RT-PCR between neonatal days 1 and 7, with this increased expression persisting into adulthood.

Regulation of the human growth hormone gene family: possible role for Pit-1 in early stages of pituitary-specific expression and repression.

The somatic cells of a multicellular organism contain an identical complement of genes that need to be expressed specifically and appropriately to allow the normal development and functions associated with an organism. In the eukaryotic cell nucleus, genes are packaged with nucleoprotein histones into chromatin. The human growth hormone (GH)/chorionic somatomammotropin (CS) gene family offers an excellent model to study the relationship between chromatin structure and transcription factor binding in terms of tissue-specific gene expression.

Hepatocyte nuclear factor-3alpha binding at P sequences of the human growth hormone locus is associated with pituitary repressor function.

The human GH family consists of five genes, including the placental chorionic somatomammotropins (CS), within a single locus on chromosome 17. Based on nuclease sensitivity, the entire GH/CS locus is accessible in pituitary chromatin, yet only GH-N is expressed. Previously, we reported a P sequence element (263P) capable of repressing placental CS-A promoter activity in transfected pituitary (GC) cells, and our data indicated a possible role for nuclear factor-1 (NF-1) and regulatory factor X1 in this repression.

Beyond angiogenesis: the cardioprotective potential of fibroblast growth factor-2.

In the field of cardiovascular research, a number of independent approaches have been explored to protect the heart from acute and chronic ischemic damage. Fibroblast growth factor-2 (FGF-2) recently has received considerable attention with respect to its angiogenic potential. While therapeutic angiogenesis may serve to salvage chronically ischemic myocardium, more acute treatments are in demand to increase cardiac resistance to injury (preconditioning) and to guard against secondary injury after an acute ischemic insult.

Transcriptional regulation of FGF-2 gene expression in cardiac myocytes.

Objective: Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium. One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix. Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection.

Biological activities of fibroblast growth factor-2 in the adult myocardium.

Fibroblast growth factor-2 (FGF-2) is a potent regulator of many cellular functions and phenomena, including cell proliferation, differentiation, survival, adhesion, migration, motility and apoptosis, and processes such as limb formation, wound healing, tumorigenesis, angiogenesis, vasculogenesis and blood vessel remodeling. In the adult myocardium, FGF-2 is expressed by various cell types, including cardiomyocytes, fibroblasts and smooth muscle cells. The biological effects of FGF-2 in the myocardium are mediated by the high-affinity tyrosine kinase receptor FGFR-1, the major FGF receptor in the heart.