Biomedical subjects

Adrian S Woolf

Publications and source records attributed to Adrian S Woolf.

39 records · Page 3Linked to original sources

PubMed2001

Galectin-3 modulates ureteric bud branching in organ culture of the developing mouse kidney.

Galectin-3 is a mammalian beta-galactoside-specific lectin with functions in cell growth, adhesion, and neoplastic transformation. On the basis of expression patterns in humans, it is proposed that galectin-3 modulates fetal collecting duct growth. This article provides evidence that galectin-3 can modulate branching morphogenesis of the mouse ureteric bud/collecting duct lineage. With the use of immunohistochemistry, galectin-3 was not detected in early metanephrogenesis but was upregulated later in fetal kidney maturation when the protein was prominent in basal domains of medullary collecting ducts. Addition of galectin-3 to embryonic days 11 and 12 whole metanephric cultures inhibited ureteric bud branching, whereas galectin-1 did not perturb morphogenesis, nor did a galectin-3 mutant lacking wild-type high-affinity binding to extended oligosaccharides. Exogenous galectin-3 retarded conversion of renal mesenchyme to nephrons in whole metanephric explants but did not affect nephron induction by spinal cord in isolated renal mesenchymes. Finally, addition of a blocking antiserum to galectin-3 caused dilation and distortion of developing epithelia in embryonic day 12 metanephroi cultured for 1 wk. The upregulation of galectin-3 protein during kidney maturation, predominantly at sites where it could mediate cell/matrix interactions, seems to modulate growth of the ureteric tree.

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PubMed2000

Angiopoietin-2 is a site-specific factor in differentiation of mouse renal vasculature.

Angiopoietin-1 (Ang-1) stimulates endothelial and vascular network differentiation through the Tie-2 receptor tyrosine kinase, while Ang-2 modulates this activation in embryo and tumor growth. The nephrogenic pattern of Ang-2 was documented in a mouse strain that expresses the LacZ reporter gene driven by the Ang-2 promoter. Heterozygous animals were healthy with morphologically normal kidneys, and they were examined after X-gal staining. At embryonic days 10.5 (E10.5) and E12.0, transgene expression was absent in the mesonephros and metanephros. At E14.0, expression was noted in the metanephric artery and its major branches. At E19.0 and in neonatal kidneys, expression was maintained in larger renal artery branches, extending to arcuate and smaller cortical vessels. Histologically, transgene expression was located in multiple layers of vessel wall cells, extending further from the endothelium than alpha-smooth muscle actin. The mesangium of immature glomeruli also expressed LacZ. In the first 3 postnatal weeks, a new pattern became evident, with intense X-gal staining in the inner stripe of the outer medulla, where a subset of thin descending limbs of loops of Henle expressed the transgene. This dynamic and developmentally regulated pattern indicates that Ang-2 is an early marker of the renal pericyte and vascular smooth muscle lineage and is also an epithelial-derived growth factor. Because Tie-2 is widely expressed by differentiating renal endothelia, this study is consistent with the hypothesis that Ang-2 has roles in kidney vascular maturation.

Angiopoietin-2↗

PubMedDate not supplied

Molecular mechanisms of human embryogenesis: developmental pathogenesis of renal tract malformations.

The focus of this review is the normal and abnormal development of the kidney and lower urinary tract; for convenience, we will refer to the whole system as the renal tract. The content represents a convergence among the clinical disciplines of histopathology, nephrology, and urology as well the basic sciences of developmental biology and molecular genetics. The story has considerable clinical relevance since diverse renal tract malformations are increasingly detected on fetal ultrasound screening and constitute major causes of chronic renal failure necessitating dialysis and kidney transplantation in children. Evidence is emerging that at least some of these disorders have a defined genetic basis; in others, an abnormal embryonic, or even maternal, environment may contribute to the pathogenesis. This field of study is frequently updated, with new discoveries being made almost every week. Hence this review can not be exhaustive or definitive, but instead highlights some specific areas of interest.

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