Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant gene-environment interactions are implicated in the pathogenesis of congenital renal dysgenesis (CRD), a leading cause of renal failure in infants and children. We have recently developed an animal model of CRD that is caused by gestational salt stress (5% NaCl diet; HS) of bradykinin B2R null mice [B2R(-/-)CRD; El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S. Physiol Genomics 3: 121-131, 2000.]. Developing B2R(-/-)CRD mice exhibit tubular and glomerular cysts, stromal expansion, and loss of corticomedullary differentiation. In addition, B2R(-/-)CRD mice exhibit transient hypertension from 2 to 4 mo of age. The present study was designed to determine the long-term consequences of CRD on renal morphology and salt sensitivity of blood pressure in B2R(-/-)CRD mice. One-year- and 18-mo-old B2R(-/-)CRD mice exhibited stunted renal growth, glomerular cystic abnormalities, and collecting duct ectasia. Moreover, tumors of mesenchymal cell origin emerged in the dysplastic kidneys of 90% of 1-yr-old and 100% of 18-mo-old B2R(-/-)CRD mice but not in age-matched B2R(-/-) or wild-type mice. When challenged with an HS diet, 18-mo-old B2R(-/-)CRD exhibited a significant rise in systolic and diastolic blood pressures and more pronounced natriuresis and diuresis compared with salt-loaded 18-mo-old wild-type mice. Kidney aquaporin-2 expression was decreased by 50%, whereas renin, ANG type 1 receptor, and Na+-K+-ATPase levels were not different in B2R(-/-)CRD mice compared with controls. In conclusion, this study demonstrates that B2R(-/-)CRD mice exhibit permanent phenotypic and functional abnormalities in renal growth and differentiation. This novel model of human disease links gene-environment interactions with renal development and blood pressure homeostasis.
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PMID:Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice. 1280 91

Kinins are vasoactive peptides that stimulate two G-protein coupled bradykinin receptors (B1R and B2R). B2R-knockout mice are salt sensitive and develop renal dysgenesis and hypertension if salt stressed during embryogenesis. B1R-knockout mice, on the other hand, are protected from inflammation and fibrosis. This study examined the spatiotemporal expression of B1R during renal organogenesis. The segmental nephron identity of B1R immunoreactivity was determined by costaining with markers of the collecting duct (Dolichos biflorus), proximal tubule (Dolichos tetraglonus), and nephron progenitors (Pax2). At E14.5, the B1R was confined to few cells in the metanephric mesenchyme. Abundance of B1R increased progressively during development. On E17.5, B1R was enriched in differentiating proximal tubular cells and by postnatal day 1, B1R was clearly expressed on the luminal aspect of the proximal tubule. Quantitative real-time PCR revealed that the levels of B1R mRNA more than double during renal maturation. We conclude that 1) B1R expression correlates closely with nephron maturation; 2) lack of B1R in nephron progenitors suggests that B1R is unlikely to play a role in early nephrogenesis; and 3) enrichment of B1R in maturing proximal tubule suggests a potential role for this receptor in terminal differentiation of the proximal nephron.
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PMID:Ontogeny of bradykinin B1 receptors in the mouse kidney. 1958 23