Vhl deletion in renal epithelia causes HIF-1 α-dependent, HIF-2α-independent angiogenesis and constitutive diuresis.
Vhl deletion in renal epithelia causes HIF-1α-dependent, HIF-2α-independent angiogenesis and constitutive diuresis. Oncotarget. 2016 Aug 12; Authors: Schönenberger D, Rajski M, Harlander S, Frew IJ Abstract One of the earliest requirements for the formation of a solid tumor is the establishment of an adequate blood supply. Clear cell renal cell carcinomas (ccRCC) are highly vascularized tumors in which the earliest genetic event is most commonly the biallelic inactivation of the VHL tumor suppressor gene, leading to constitutive activation of the HIF-1α and HIF-2α transcription factors, which are known angiogenic factors. However it remains unclear whether either or both HIF-1α or HIF-2α stabilization in normal renal epithelial cells are necessary or sufficient for alterations in blood vessel formation. We show that renal epithelium-specific deletion of Vhl in mice causes increased medullary vascularization and that this phenotype is completely rescued by Hif1a co-deletion, but not by co-deletion of Hif2a. A physiological consequence of changes in the blood vessels of the vasa recta in Vhl-deficient mice is a diabetes insipidus phenotype of excretion of large amounts of highly diluted urine. This constitutive diuresis is fully compensated by increased water consumption and mice do not show any signs of dehydration, renal failure or salt wasting and blood electrolyte levels remain unchanged. Co-deletion of Hif1a, bu...
CONCLUSIONS: The average patient is middle aged (often male) with a history of subacute back pain, sometimes presenting fever and/or neurological damage on diagnosis. Acute phase reactants are frequently raised. Diabetes mellitus, endocarditis and immunosuppressed patients may have the worst chance of a good outcome, therefore these patients should be more carefully managed (always try to obtain an imaging-guided biopsy, correct antibiotic treatment, and a functional and clinical follow-up). PMID: 32446680 [PubMed - as supplied by publisher]
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This study, for instance, attributes a patient’s waitlist/transplant outcome to the very last dialysis facility the patient was associated with. In epidemiology speak, this means the causal inference authors are trying to draw between for-profit status and good transplant outcomes is subject to time-varying confounding. As an example, if one is seeking an association between testosterone levels and risk of a heart attack, using the last testosterone level available would be a poor way of doing this study because testosterone levels are known to vary over time. The same applies to dialysis facilities. Patie...
Publication date: 5 August 2020Source: Journal of Pharmaceutical and Biomedical Analysis, Volume 187Author(s): Valentina Iacuzzi, Martina Zanchetta, Sara Gagno, Ariana Soledad Poetto, Marco Orleni, Elena Marangon, Michela Guardascione, Luisa Foltran, Bianca Posocco, Giuseppe Toffoli
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