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Pathogenic pathways are activated in each major cell type of the glomerulus in the Cd2ap mutant mouse model of focal segmental glomerulosclerosis

Overview of attention for article published in BMC Nephrology, May 2015
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Title
Pathogenic pathways are activated in each major cell type of the glomerulus in the Cd2ap mutant mouse model of focal segmental glomerulosclerosis
Published in
BMC Nephrology, May 2015
DOI 10.1186/s12882-015-0063-z
Pubmed ID
Authors

Eric W. Brunskill, S. Steven Potter

Abstract

Mutations in several genes expressed in podocytes, including Cd2ap, have been associated with focal segmental glomerulosclerosis in humans. Mutant mouse models provide an opportunity to better understand the molecular pathology that drives these diseases. In this report we use a battery of transgenic-GFP mice to facilitate the purification of all three major cell types of the glomerulus from Cd2ap mutant mice. Both microarrays and RNA-seq were used to characterize the gene expression profiles of the podocytes, mesangial cells and endothelial cells, providing a global dual platform cross-validating dataset. The mesangial cells showed increased expression of profibrotic factors, including thrombospondin, Tgfb2 and Tgfb3, as well as the angiogenesis factor Vegf. They also showed upregulation of protective genes, including Aldh1a2, involved in retinoic acid synthesis and Decorin, a Tgfb antagonist. Of interest, the mesangial cells also showed significant expression of Wt1, which has generally been considered podocyte specific. The Cd2ap mutant podocytes showed upregulation of proteases as well as genes involved in muscle and vasculature development and showed a very strong gene expression signature indicating programmed cell death. Endothelial cells showed increased expression of the leukocyte adhesion associated factors Vcam1 and Sele, as well as Midkine (promoting angiogenesis), endothelin and many genes responsive to cytokines and interferons. This study provides a comprehensive analysis of the changing properties of the three cell types of the glomerulus in Cd2ap mutants, identifying activated and repressed pathways and responsible genes, thereby delivering a deeper molecular understanding of this genetic disease.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 4%
Unknown 26 96%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 26%
Researcher 7 26%
Other 4 15%
Student > Bachelor 1 4%
Professor > Associate Professor 1 4%
Other 0 0%
Unknown 7 26%
Readers by discipline Count As %
Medicine and Dentistry 7 26%
Agricultural and Biological Sciences 6 22%
Biochemistry, Genetics and Molecular Biology 4 15%
Pharmacology, Toxicology and Pharmaceutical Science 2 7%
Computer Science 2 7%
Other 1 4%
Unknown 5 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 May 2015.
All research outputs
#17,756,606
of 22,803,211 outputs
Outputs from BMC Nephrology
#1,702
of 2,465 outputs
Outputs of similar age
#179,495
of 264,552 outputs
Outputs of similar age from BMC Nephrology
#36
of 46 outputs
Altmetric has tracked 22,803,211 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,465 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,552 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.