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Find video protocols related to scientific articles indexed in Pubmed.
Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.
PLoS ONE
PUBLISHED: 01-01-2014
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Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs) and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.
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Bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth.
PLoS ONE
PUBLISHED: 01-01-2013
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The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.
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Serial renal biopsy findings in a case of POEMS syndrome with recurrent acute renal failure.
Clin. Exp. Nephrol.
PUBLISHED: 09-01-2011
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This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case.
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Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.
J. Clin. Invest.
PUBLISHED: 02-08-2010
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The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.
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[Case of kidney failure with thrombotic microangiopathy lesions in renal biopsy caused by accelerated hypertension in young adult].
Nihon Jinzo Gakkai Shi
PUBLISHED: 11-26-2009
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A 19-year-old male was admitted to our hospital for the treatment of severe hypertension with renal dysfunction. Two years before admission, his hypertension had been diagnosed as essential hypertension based on a series of examinations when his renal function was not impaired. Visits to his primary physician ended when he developed severe hypertension of 210/140 mmHg, at which time renal dysfunction and serum creatinine of 2.25 mg/dL were discovered. Renin and antidiuretic hormone were slightly elevated, but renal artery stenosis or other abnormalities were not detected by magnetic resonance imaging and computer tomography. After the hypertension was controlled by medication, a renal biopsy was performed to assess renal impairment. Histology demonstrated lesions compatible with thrombotic microangiopathy (TMA) and ischemic lesions, including fibrinoid necrosis, intimal thickening, occlusion in the small arteries, wrinkling and duplication of the glomerular basement membrane with microthrombi, and focal interstitial fibrosis. Renal function ameliorated after the hypertension was controlled. This case suggests that severe and accelerated hypertension can cause TMA with renal impairment even in young people.
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Direct hematological toxicity and illegitimate chromosomal recombination caused by the systemic activation of CreERT2.
J. Immunol.
PUBLISHED: 04-22-2009
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The CreER(T2) for conditional gene inactivation has become increasingly used in reverse mouse genetics, which enables temporal regulation of Cre activity using a mutant estrogen binding domain (ER(T2)) to keep Cre inactive until the administration of tamoxifen. In this study, we present the severe toxicity of ubiquitously expressed CreER(T2) in adult mice and embryos. The toxicity of Cre recombinase or CreER(T2) in vitro or in vivo organisms are still less sufficiently recognized considering the common use of Cre/loxP system, though the toxicity might compromise the phenotypic analysis of the gene of interest. We analyzed two independent lines in which CreER(T2) is knocked-in into the Rosa26 locus (R26CreER(T2) mice), and both lines showed thymus atrophy, severe anemia, and illegitimate chromosomal rearrangement in hematopoietic cells after the administration of tamoxifen, and demonstrated complete recovery of hematological toxicity in adult mice. In the hematopoietic tissues in R26CreER(T2) mice, reduced proliferation and increased apoptosis was observed after the administration of tamoxifen. Flow cytometric analysis revealed that CreER(T2) toxicity affected several hematopoietic lineages, and that immature cells in these lineages tend to be more sensitive to the toxicity. In vitro culturing of hematopoietic cells from these mice further demonstrated the direct toxicity of CreER(T2) on growth and differentiation of hematopoietic cells. We further demonstrated the cleavage of the putative cryptic/pseudo loxP site in the genome after the activation of CreER(T2) in vivo. We discussed how to avoid the misinterpretation of the experimental results from potential toxic effects due to the activated CreER(T2).
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.