Cerebral ischemia in heme oxygenase-2-deficient mice: the second filament makes the difference.
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Animals↗
Biomedical subjects
Nicole Wagner
Publications and source records attributed to Nicole Wagner.
Early prevention of obesity and cardiovascular diseases.
SUMMARY: The prevalence of nutrition related diseases increased exponentially during the last decades. Risk factors are acquired early in life. Preventive measures include a longer duration of breast-feeding and measures of prevention and health promotion early in childhood. These measures should be undertaken by all persons having influence on the development of children.
Adolescent↗
Two selective novel triterpene glycosides from sea cucumber, Telenata Ananas: inhibitors of chemokine receptor-5.
The aqueous methanolic extract of a sea cucumber was found to contain two triterpene glycosides 1 and 2. The structures of 1 and 2 were established based on high-resolution NMR studies. Compounds 1 and 2 exhibited inhibitory activity (K(i)) of 30 and 5microM, respectively, in a chemokine receptor subtype 5 (CCR5) assay. Both compounds did not show any significant inhibition in a CXCR2 assay at 50microM, suggesting their selectivity for the CCR5 receptor.
Animals↗
The Wilms' tumor suppressor Wt1 is expressed in the coronary vasculature after myocardial infarction.
Expression of the Wilms' tumor gene Wt1 in the epicardium is critical for normal heart development. Mouse embryos with inactivated Wt1 gene have extremely thin ventricles, which can result in heart failure and death. Here, we demonstrate that Wt1 can be activated in adult hearts by local ischemia. Wt1 mRNA was increased more than twofold in the left ventricular myocardium of rats between 1 day and 9 wk after infarction. Wt1 expression was localized by means of mRNA in situ hybridization and immunohistochemistry to vascular endothelial and vascular smooth muscle cells in the border zone of the infarcted tissue. A strikingly similar distribution was seen for vascular endothelial growth factor and two different cell proliferation markers in the coronary vessels of the ischemic heart. No Wt1 could be detected in the vasculature of the noninfarcted right ventricles. Wt1 expression in the coronary vessels of the ischemic heart was mimicked by exposure of rats to normobaric hypoxia (8% O2) and 0.1% CO, respectively. These findings demonstrate that Wt1 is expressed in the vasculature of the heart in response to local ischemia and hypoxia. They suggest that Wt1 has a role in the growth of coronary vessels after myocardial infarction.
Animals↗
The Wilms' tumor gene Wt1 is required for normal development of the retina.
The Wilms' tumor gene Wt1 is known for its important functions during genitourinary and mesothelial formation. Here we show that Wt1 is necessary for neuronal development in the vertebrate retina. Mouse embryos with targeted disruption of Wt1 exhibit remarkably thinner retinas than age-matched wild-type animals. A large fraction of retinal ganglion cells is lost by apoptosis, and the growth of optic nerve fibers is severely disturbed. Strikingly, expression of the class IV POU-domain transcription factor Pou4f2 (formerly Brn-3b), which is critical for the survival of most retinal ganglion cells, is lost in Wt1(-/-) retinas. Forced expression of Wt1 in cultured cells causes an up-regulation of Pou4f2 mRNA. Moreover, the Wt1(-KTS) splice variant can activate a reporter construct carrying 5'-regulatory sequences of the human POU4F2. The lack of Pou4f2 and the ocular defects in Wt1(-/-) embryos are rescued by transgenic expression of a 280 kb yeast artificial chromosome carrying the human WT1 gene. Taken together, our findings demonstrate a continuous requirement for Wt1 in normal retina formation with a critical role in Pou4f2-dependent ganglion cell differentiation.
Animals↗
The Wilms' tumor suppressor Wt1 is associated with the differentiation of retinoblastoma cells.
We have demonstrated recently that Wilms' tumor suppressor 1 (Wt1),in addition to its role in genitourinary formation,is required for the differentiation of ganglion cells in the developing retina. Here we provide further evidence that Wt1 is associated with neuronal differentiation. Thus, the retinoblastoma-derived human cell line, Y-79, contained robust amounts of Wt1 mRNA and protein. Wt1 expression was down-regulated upon laminin-induced differentiation of Y-79 into neuron-like cells. Inhibition of Wt1 with antisense oligonucleotides dramatically reduced the capacity of undifferentiated Y-79 cells to undergo neuronal differentiation, whereas sense and missense oligonucleotides had no effect. Wt1 immunoreactivity was also detected in solid retinoblastomas, in which it resided mainly in areas with moderate proliferative activity. These findings suggest a role for Wt1 in the differentiation of retinoblastoma cells. Furthermore, Wt1 expression in retinoblastoma may reflect the potential of these tumors to initiate the early steps of neuronal differentiation.
Cell Differentiation↗
Activation of vitamin D receptor by the Wilms' tumor gene product mediates apoptosis of renal cells.
The Wilms' tumor transcription factor WT1 is required for kidney development, but little is known about WT1 downstream signaling in renal cells. This study reported an approximately fivefold upregulation of vitamin D receptor (VDR) mRNA and protein in human embryonic kidney (HEK) 293 cells that stably expressed WT1 at a level comparable to the developing kidney in vivo. Co-transfection of HEK 293 cells with expression plasmids encoding four different WT1 splicing variants stimulated mouse vdr promoter activity more than fourfold. A 201-bp fragment was identified in the proximal vdr promoter that was required for transactivation by WT1. This critical sequence contained a predicted WT1 consensus site, which bound to recombinant WT1 protein. Temporal changes of vdr and wt1 mRNA levels in developing rat kidneys were correlated closely. The active metabolite 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) strongly inhibited the proliferation of wt1-transfected HEK 293 cells. Exposure to 1,25-(OH)(2)D(3) caused apoptosis of cultured wt1 immunopositive cells from mouse embryonic kidney cortex. These findings suggest that transcriptional activation of the VDR by WT1 can mediate programmed death of renal embryonic cells in response to 1,25-(OH)(2)D(3). The results provide the first evidence for a role of the vitamin D endocrine system in renal cell growth and differentiation during development.
Animals↗