Oxytocin Modulates Expression and Trafficking of Aquaporins
The administrationof oxytocin to induce labor in pregnancy is associated withhyponatremia, but the mechanisms underlying the retention ofwater are incompletely understood. Li et al. infused oxytocinfor 5 d into vasopressin-deficient rats and observed that oxytocinacts through vasopression (V2) receptors on the principal cellsof the collecting duct to increase the expression and traffickingof aquaporin-2 and aquaporin-3. These results raise the intriguingpossibility of treating severe oxytocin-induced hyponatremiawith V2 receptor antagonists, which would not affect oxytocin-mediateduterine contractions. See Li et al., pages 225–232.
The Glomerulus Meets Systems Biology
Our knowledgeof the roles of glomerular proteins in the pathophysiology ofdisease is limited. He et al. used bioinformatics and an integrativesystems biology approach to unravel the complex network of glomerularproteins. By combining published and original data regardingthe glomerular transcriptome, the authors created a catalogof glomerulus-enriched genes and constructed a model of predictedprotein–protein interactions. This comprehensive analysisof the glomerular transcriptome may facilitate the study ofthe roles of glomerular proteins in health and disease. SeeHe et al., pages 260–268.
Does obesityhurt one's chances for receiving a kidney transplant? Segevet al. analyzed data from a prospective cohort of >130,000patients who were registered for transplantation in the UnitedStates and revealed an independent negative association betweenbody mass index (BMI) and likelihood of transplantation. Themorbidly obese are 44% less likely to receive a transplant thanthose with normal BMI, and when an organ becomes available,providers are more likely to bypass an obese potential recipientin favor of one with a lower BMI. This calls for further scrutinyof the apparent bias against the obese in kidney transplantation.See Segev et al., pages 349–355.
Steroid-resistantnephrotic syndrome can be caused by mutations in the gene encodingpodocin (NPHS2). In a worldwide cohort study involving 430 affectedchildren, Hinkes et al. identified a genotype–phenotypecorrelation between NPHS2 mutations and age of onset of disease.The mean age of onset among children who had at least one truncationmutation or who were homozygous for the R138Q mutation was <2yr. All other types of podocin mutations correlated with a meanage of onset of >4 yr. Even among those with identical mutations,however, age of onset varied by several years, suggesting thepresence of additional disease modifiers. See Hinkes et al.,pages 365–371.
ADMA, Proteinuria, and Endothelial Dysfunction
Asymmetricdimethyl-arginine (ADMA), a breakdown product of arginine-methylatedproteins, is a potent inhibitor of nitric oxide synthase. Yilmazet al. report that serum levels of ADMA are higher in non-diabeticpatients with proteinuria than in age-, sex-, and body massindex–matched healthy control subjects. This finding isparticularly prominent among those with secondary amyloidosis,who are known to have increased protein turnover. Moreover,ADMA level is an independent predictor of endothelial dysfunction,providing a potential mechanistic link between proteinuria andcardiovascular morbidity and mortality. See Yilmaz et al., pages388–395.
Goodpasture T Cells May Exist in All of Us
AutoreactiveT cells play a role in the pathogenesis of Goodpasture disease,but it is unknown how these cells escape tolerance mechanisms.Zou et al. hypothesized that proteases normally destroy theGoodpasture autoantigen before the immune system ever has achance to recognize it as "self." To test their hypothesis,the authors searched for quiescent 3(IV)NC1-specific T cellsin healthy volunteers and found them in all. Furthermore, theyshow that the endosomal enzymes cathepsin D and E are likelyresponsible for the destructive processing of the Goodpastureautoantigen. These results suggest that peptide susceptibilityto proteolytic cleavage may be a major determinant of T cellspecificity in autoimmune disease. See Zou et al., pages 396–404.
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Molecular Mechanisms of Antidiuretic Effect of Oxytocin
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J. Am. Soc. Nephrol. 2008 19: 225-232.
[Abstract][Full Text][PDF]
Specific Podocin Mutations Correlate with Age of Onset in Steroid-Resistant Nephrotic Syndrome
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ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction
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Healthy Individuals Have Goodpasture Autoantigen-Reactive T Cells
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The Glomerular Transcriptome and a Predicted Protein–Protein Interaction Network
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J. Am. Soc. Nephrol. 2008 19: 260-268.
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Obesity Impacts Access to Kidney Transplantation
Dorry L. Segev, Christopher E. Simpkins, Richard E. Thompson, Jayme E. Locke, Daniel S. Warren, and Robert A. Montgomery
J. Am. Soc. Nephrol. 2008 19: 349-355.
[Abstract][Full Text][PDF]
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BASIC RESEARCH
CLINICAL EPIDEMIOLOGY
3(IV)NC1-specific T cells in healthy volunteers and found them in all. Furthermore, they show that the endosomal enzymes cathepsin D and E are likely responsible for the destructive processing of the Goodpasture autoantigen. These results suggest that peptide susceptibility to proteolytic cleavage may be a major determinant of T cell specificity in autoimmune disease. See Zou et al., pages 396–404. 
