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Sökning: WFRF:(Pisetsky D)

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  • Crowley, S. D., et al. (författare)
  • Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis
  • 2009
  • Ingår i: J Clin Invest. - 1558-8238 .- 1558-8238 .- 0021-9738. ; 119:4, s. 943-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
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  • Woolf, Anthony D., et al. (författare)
  • Clinical advances – from bench to bedside
  • 2020
  • Ingår i: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 34:5
  • Forskningsöversikt (refereegranskat)
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