Frances Cousins

Transforming growth factor beta 1 (TGF beta 1) is shown here to be required for yolk sac haematopoiesis and endothelial differentiation. Mice with a targeted mutation in the TGF beta 1 gene were examined to determine the cause of prenatal lethality, which occurs in 50% of homozygous TGF beta 1 null (TGF beta 1-/-) conceptions. 50% of TGF beta 1-/- and 25% of TGF beta 1-+-) conceptions. 50% of TGF beta 1-/- and 25% of TGF beta 1+/- conceptuses were found to die at around 10.5 dpc. The primary defects were restricted to extraembryonic tissues, namely the yolk sac vasculature and haematopoietic system. The embryos per se showed developmental retardation, oedema and necrosis, which were probably secondary to the extraembryonic lesions. The defect in vasculogenesis appeared to affect endothelial differentiation, rather than the initial appearance and outgrowth of endothelial cells. Initial differentiation of yolk sac mesoderm to endothelial cells occurred, but defective differentiation resulted in inadequate capillary tube formation, and weak vessels with reduced cellular adhesiveness. Defective haematopoiesis resulted in a reduced erythroid cell number within the yolk sac. Defective yolk sac vasculogenesis and haematopoiesis were present either together, or in isolation of each other. The phenotypes are consistent with the observation of abundant TGF beta 1 gene expression in both endothelial and haematopoietic precursors. The data indicate that the primary effect of loss of TGF beta 1 function in vivo is not increased haematopoietic or endothelial cell proliferation, which might have been expected by deletion of a negative growth regulator, but defective haematopoiesis and endothelial differentiation.

Transforming growth factor-beta 1 (TGF-beta 1) is a modulator of cellular proliferation, differentiation, and extracellular matrix deposition. It is a potent epithelial growth inhibitor and can alter the differentiative properties of keratinocytes, in vitro, but little is known about its normal physiological function in the epidermis in vivo. Transgenic mice were generated using a keratin 10 (K10) gene promoter to drive constitutive expression of TGF-beta 1 in the suprabasal keratinocyte compartment. Surprisingly, these mice showed a two- to threefold increase in epidermal DNA labeling index over control mice, in the absence of hyperplasia. The transgene, however, acted in the expected fashion, as a negative regulator of cell growth, when hyperplasia was induced by treatment by 12-tetradecanoyl-phorbol-13-acetate (TPA). Epidermal TGF-beta type I and II receptor (T beta RI and T beta RII) levels were examined in control and transgenic mice during induction of hyperplasia by TPA. Whereas T beta RI levels remained relatively constant, T beta RII expression was strongly induced in TPA-treated skins, prior to the induction of the growth inhibitory response to TGF-beta 1, and its level of expression correlated with growth sensitivity to TGF-beta 1 in vivo and in vitro. These results suggest that TGF-beta 1 and its type II receptor are part of the endogenous homeostatic regulatory machinery of the epidermis.

Iodine insufficiency is now a prominent issue in the UK and other European countries due to low intakes of dairy products and seafood (especially where iodine fortification is not in place). In the present study, we tested a commercially available encapsulated edible seaweed (Napiers Hebridean Seagreens® Ascophyllum nodosum species) for its acceptability to consumers and iodine bioavailability and investigated the impact of a 2-week daily seaweed supplementation on iodine concentrations and thyroid function. Healthy non-pregnant women of childbearing age, self-reporting low dairy product and seafood consumption, with no history of thyroid or gastrointestinal disease were recruited. Seaweed iodine (712 μg, in 1 g seaweed) was modestly bioavailable at 33 (interquartile range (IQR) 28-46) % of the ingested iodine dose compared with 59 (IQR 46-74) % of iodine from the KI supplement (n 22). After supplement ingestion (2 weeks, 0·5 g seaweed daily, n 42), urinary iodine excretion increased from 78 (IQR 39-114) to 140 (IQR 103-195) μg/l (P< 0·001). The concentrations of thyroid-stimulating hormone increased from 1·5 (IQR 1·2-2·2) to 2·1 (IQR 1·3-2·9) mIU/l (P< 0·001), with two participants having concentrations exceeding the normal range after supplement ingestion (but normal free thyroxine concentrations). There was no change in the concentrations of other thyroid hormones after supplement ingestion. The seaweed was palatable and acceptable to consumers as a whole food or as a food ingredient and effective as a source of iodine in an iodine-insufficient population. In conclusion, seaweed inclusion in staple foods would serve as an alternative to fortification of salt or other foods with KI.