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Selective pharmacological inhibition of DDR1 prevents experimentally-induced glomerulonephritis in prevention and therapeutic regime

Overview of attention for article published in Journal of Translational Medicine, June 2018
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Title
Selective pharmacological inhibition of DDR1 prevents experimentally-induced glomerulonephritis in prevention and therapeutic regime
Published in
Journal of Translational Medicine, June 2018
DOI 10.1186/s12967-018-1524-5
Pubmed ID
Authors

Solange Moll, Yukari Yasui, Ahmed Abed, Takeshi Murata, Hideaki Shimada, Akira Maeda, Naoshi Fukushima, Masakazu Kanamori, Sabine Uhles, Laura Badi, Thomas Cagarelli, Ivan Formentini, Faye Drawnel, Guy Georges, Tobias Bergauer, Rodolfo Gasser, R. Daniel Bonfil, Rafael Fridman, Hans Richter, Juergen Funk, Marcus J. Moeller, Christos Chatziantoniou, Marco Prunotto

Abstract

Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase extensively implicated in diseases such as cancer, atherosclerosis and fibrosis. Multiple preclinical studies, performed using either a gene deletion or a gene silencing approaches, have shown this receptor being a major driver target of fibrosis and glomerulosclerosis. The present study investigated the role and relevance of DDR1 in human crescentic glomerulonephritis (GN). Detailed DDR1 expression was first characterized in detail in human GN biopsies using a novel selective anti-DDR1 antibody using immunohistochemistry. Subsequently the protective role of DDR1 was investigated using a highly selective, novel, small molecule inhibitor in a nephrotoxic serum (NTS) GN model in a prophylactic regime and in the NEP25 GN mouse model using a therapeutic intervention regime. DDR1 expression was shown to be mainly limited to renal epithelium. In humans, DDR1 is highly induced in injured podocytes, in bridging cells expressing both parietal epithelial cell (PEC) and podocyte markers and in a subset of PECs forming the cellular crescents in human GN. Pharmacological inhibition of DDR1 in NTS improved both renal function and histological parameters. These results, obtained using a prophylactic regime, were confirmed in the NEP25 GN mouse model using a therapeutic intervention regime. Gene expression analysis of NTS showed that pharmacological blockade of DDR1 specifically reverted fibrotic and inflammatory gene networks and modulated expression of the glomerular cell gene signature, further validating DDR1 as a major mediator of cell fate in podocytes and PECs. Together, these results suggest that DDR1 inhibition might be an attractive and promising pharmacological intervention for the treatment of GN, predominantly by targeting the renal epithelium.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 30%
Student > Ph. D. Student 3 13%
Professor > Associate Professor 2 9%
Student > Doctoral Student 1 4%
Librarian 1 4%
Other 3 13%
Unknown 6 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 17%
Medicine and Dentistry 4 17%
Agricultural and Biological Sciences 3 13%
Social Sciences 1 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Other 2 9%
Unknown 8 35%

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 03 June 2018.
All research outputs
#10,391,435
of 13,028,155 outputs
Outputs from Journal of Translational Medicine
#2,225
of 2,587 outputs
Outputs of similar age
#203,284
of 271,352 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 13,028,155 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,587 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one is in the 8th percentile – i.e., 8% 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 271,352 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them