Life Without Nephrin

Miner, Jeffrey H.

doi:10.1681/asn.2012010016

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…Genomic analysis revealed that the developing chick genome lacks nephrin and nephroproteins, whereas the structure of the slit diaphragms of podocyte FPs is maintained. 42 In the present study, plasma levels of creatinine (measured as an index for glomerular filtration rate), electrolytes and osmolality are similar between CT and EwW quail, suggesting that renal function is not impaired at this stage in spite of morphological injury of glomerular mesangium.…”

Section: Role Of Mesangium In Reduced Nutrition-induced Renal Injurysupporting

confidence: 55%

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail

Nishimura

Yaoita

Nameta

et al. 2017

J Dev Orig Health Dis

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Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail, Coturnix japonica, in which partial (8-10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins, N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for 'fetal programming,' which appears to have evolved phylogenetically early.

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Section: Role Of Mesangium In Reduced Nutrition-induced Renal Injurysupporting

confidence: 55%

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail

Nishimura

Yaoita

Nameta

et al. 2017

J Dev Orig Health Dis

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“…Others have questioned the central role of nephrin in guiding, forming, and maintaining the slit diagram on the basis of the observation that birds lack an ortholog of NPHS1 but still form slit diagram within their kidneys and can retain serum albumin in their blood. 3,42,43 So perhaps, as previously suggested by others, 3,42 it is not nephrin per se that is critical for preventing proteinuria but the slit diagram itself that is required to maintain the glomerular ultrafilter. Consistent with this hypothesis, slit diagrams were observed in mice with .80% nephrin depletion.…”

Section: Discussionmentioning

confidence: 90%

Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Chuang

D’Agati

et al. 2015

Journal of the American Society of Nephrology

102

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Nephrin is required during kidney development for the maturation of podocytes and formation of the slit diaphragm junctional complex. Because nephrin expression is downregulated in acquired glomerular diseases, nephrin deficiency is considered a pathologic feature of glomerular injury. However, whether nephrin deficiency exacerbates glomerular injury in glomerular diseases has not been experimentally confirmed. Here, we generated mice with inducible RNA interference-mediated nephrin knockdown. Short-term nephrin knockdown (6 weeks), starting after the completion of kidney development at 5 weeks of age, did not affect glomerular structure or function. In contrast, mice with long-term nephrin knockdown (20 weeks) developed mild proteinuria, foot process effacement, filtration slit narrowing, mesangial hypercellularity and sclerosis, glomerular basement membrane thickening, subendothelial zone widening, and podocyte apoptosis. When subjected to an acquired glomerular insult induced by unilateral nephrectomy or doxorubicin, mice with short-term nephrin knockdown developed more severe glomerular injury compared with mice without nephrin knockdown. Additionally, nephrin-knockdown mice developed more exaggerated glomerular enlargement when subjected to unilateral nephrectomy and more podocyte apoptosis and depletion after doxorubicin challenge. AKT phosphorylation, which is a slit diaphragm-mediated and nephrin-dependent pathway in the podocyte, was markedly reduced in mice with long-term or short-term nephrin knockdown challenged with uninephrectomy or doxorubicin. Taken together, our data establish that under the basal condition and in acquired glomerular diseases, nephrin is required to maintain slit diaphragm integrity and slit diaphragm-mediated signaling to preserve glomerular function and podocyte viability in adult mice.

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“…These genes possibly reflect traits that are specific to birds. As an intriguing example, NPHS1 , which results in kidney nephrosis and disruption of the glomerular filtration barrier when functionally knocked out in humans, and KIRREL2 , which is expressed in kidney and encodes the slit diaphragm protein Neph2/filtrin [ 38 , 39 ], are both missing in birds, possibly leading to a reduced control of glomerular filtration rates compared to mammals. These cases would help explain the lower capacity of birds to concentrate urine under a hyperosmotic challenge, and could relate to the emergence of the birds’ ability to regulate water/electrolyte balance by modulating water release from red blood cells [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Conserved syntenic clusters of protein coding genes are missing in birds

et al. 2014

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BackgroundBirds are one of the most highly successful and diverse groups of vertebrates, having evolved a number of distinct characteristics, including feathers and wings, a sturdy lightweight skeleton and unique respiratory and urinary/excretion systems. However, the genetic basis of these traits is poorly understood.ResultsUsing comparative genomics based on extensive searches of 60 avian genomes, we have found that birds lack approximately 274 protein coding genes that are present in the genomes of most vertebrate lineages and are for the most part organized in conserved syntenic clusters in non-avian sauropsids and in humans. These genes are located in regions associated with chromosomal rearrangements, and are largely present in crocodiles, suggesting that their loss occurred subsequent to the split of dinosaurs/birds from crocodilians. Many of these genes are associated with lethality in rodents, human genetic disorders, or biological functions targeting various tissues. Functional enrichment analysis combined with orthogroup analysis and paralog searches revealed enrichments that were shared by non-avian species, present only in birds, or shared between all species.ConclusionsTogether these results provide a clearer definition of the genetic background of extant birds, extend the findings of previous studies on missing avian genes, and provide clues about molecular events that shaped avian evolution. They also have implications for fields that largely benefit from avian studies, including development, immune system, oncogenesis, and brain function and cognition. With regards to the missing genes, birds can be considered ‘natural knockouts’ that may become invaluable model organisms for several human diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0565-1) contains supplementary material, which is available to authorized users.

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Life Without Nephrin

Cited by 14 publications

References 35 publications

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail

Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Conserved syntenic clusters of protein coding genes are missing in birds

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