• MeSH
• alfa-galaktosidasa genetika   terapeutické užití   MeSH
• časná diagnóza MeSH
• diferenciální diagnóza MeSH
• enzymová substituční terapie metody   MeSH
• Fabryho nemoc * enzymologie   farmakoterapie   genetika   MeSH
• kardiomegalie genetika   MeSH
• lidé MeSH
• neuralgie genetika   MeSH
• proteinurie genetika   MeSH
• Check Tag
• lidé MeSH

The main manifestations of nephrotic syndrome include proteinuria, hypoalbuminemia, edema, hyperlipidemia and lipiduria. Common causes of nephrotic syndrome are diabetic nephropathy, minimal change disease (MCD), focal and segmental glomerulosclerosis (FSGS) and membranous nephropathy. Among the primary glomerular diseases, MCD is usually sensitive to glucocorticoid treatment, whereas the other diseases show variable responses. Despite the identification of key structural proteins in the glomerular capillary loop which may contribute to defects in ultrafiltration, many of the disease mechanisms of nephrotic syndrome remain unresolved. In this study, we show that the glomerular expression of angiopoietin-like-4 (Angptl4), a secreted glycoprotein, is glucocorticoid sensitive and is highly upregulated in the serum and in podocytes in experimental models of MCD and in the human disease. Podocyte-specific transgenic overexpression of Angptl4 (NPHS2-Angptl4) in rats induced nephrotic-range, and selective, proteinuria (over 500-fold increase in albuminuria), loss of glomerular basement membrane (GBM) charge and foot process effacement, whereas transgenic expression specifically in the adipose tissue (aP2-Angptl4) resulted in increased circulating Angptl4, but no proteinuria. Angptl4(-/-) mice that were injected with lipopolysaccharide (LPS) or nephritogenic antisera developed markedly less proteinuria than did control mice. Angptl4 secreted from podocytes in some forms of nephrotic syndrome lacks normal sialylation. When we fed the sialic acid precursor N-acetyl-D-mannosamine (ManNAc) to NPHS2-Angptl4 transgenic rats it increased the sialylation of Angptl4 and decreased albuminuria by more than 40%. These results suggest that podocyte-secreted Angptl4 has a key role in nephrotic syndrome.

• MeSH
• albuminurie MeSH
• angiopoetiny genetika   metabolismus   MeSH
• financování organizované MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• nefrotický syndrom moč   patofyziologie   MeSH
• potkani transgenní MeSH
• proteinurie genetika   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH

Our previous studies in heterozygous Ren-2 transgenic rats (TGR) have shown that early treatment with selective endothelin (ET)(A) receptor blockade is superior to nonselective ET(A/B) receptor blockade. The aim of this study was to evaluate the role of the ET system in male heterozygous TGR with established hypertension (late-onset treatment). TGR and control Hannover Sprague-Dawley (HanSD) rats were fed a high-salt diet and were treated concomitantly with the nonselective ET(A/B) receptor blocker bosentan or the selective ET(A) receptor blocker atrasentan from day 52 of age on. Survival rate was partly increased by bosentan and fully normalized with atrasentan. Bosentan transiently decreased blood pressure (BP), whereas atrasentan significantly reduced BP as early as one week after the start of the treatment. This effect persisted for the whole experimental period. Atrasentan also substantially reduced cardiac hypertrophy, proteinuria, glomerulosclerosis and left ventricle ET-1 content. Bosentan improved and atrasentan almost restored podocyte architecture and reversed changes in podocyte phenotype represented by the expression of CD 10, desmin and vimentin. Our results demonstrate that selective ET(A) receptor blockade has more favorable effects than nonselective ET(A/B) receptor blockade and, unlike observed in homozygous TGR, ET(A) receptor blockade has similar effects in heterozygous rats with established hypertension as in young animals with developing hypertension.

• MeSH
• angiotensin II fyziologie   MeSH
• antagonisté endotelinového receptoru MeSH
• elektronová mikroskopie MeSH
• endotelin-1 metabolismus   MeSH
• financování organizované MeSH
• fokálně segmentální glomeruloskleróza patologie   MeSH
• geneticky modifikovaná zvířata MeSH
• heterozygot MeSH
• hypertenze maligní farmakoterapie   genetika   patologie   MeSH
• imunohistochemie MeSH
• krevní tlak genetika   účinky léků   MeSH
• krysa rodu rattus MeSH
• ledviny patologie   MeSH
• míra přežití MeSH
• potkani Sprague-Dawley MeSH
• proteinurie genetika   MeSH
• receptory endotelinů MeSH
• renin fyziologie   genetika   MeSH
• sodík dietní farmakologie   MeSH
• tělesná hmotnost genetika   MeSH
• velikost orgánu genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• angiotensin II genetika   imunologie   MeSH
• glomerulární bazální membrána fyziologie   patofyziologie   MeSH
• glomerulonefritida etiologie   patofyziologie   MeSH
• kapilární permeabilita fyziologie   imunologie   účinky léků   MeSH
• lidé MeSH
• membranózní glomerulonefritida etiologie   imunologie   patofyziologie   MeSH
• nemoci imunitního systému etiologie   imunologie   patofyziologie   MeSH
• podocyty cytologie   fyziologie   MeSH
• proteinurie genetika   imunologie   moč   MeSH
• receptory vaskulárního endoteliálního růstového faktoru genetika   imunologie   MeSH
• Check Tag
• lidé MeSH