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Inhibition of (pro)renin Receptor Contributes to Renoprotective Effects of Angiotensin II Type 1 Receptor Blockade in Diabetic Nephropathy

Overview of attention for article published in Frontiers in Physiology, October 2017
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Title
Inhibition of (pro)renin Receptor Contributes to Renoprotective Effects of Angiotensin II Type 1 Receptor Blockade in Diabetic Nephropathy
Published in
Frontiers in Physiology, October 2017
DOI 10.3389/fphys.2017.00758
Pubmed ID
Authors

Lin Zhang, Xiao-Fei An, Xin Ruan, Dong-Dong Huang, Li Zhou, Hong Xue, Li-Min Lu, Ming He

Abstract

Aims: Renal renin-angiotensin system (RAS) plays a pivotal role in the development of diabetic nephropathy (DN). Angiotensin II (Ang II) type 1 receptor (AT1R) blockade elevates (pro)renin, which may bind to (pro)renin receptor (PRR) and exert receptor-mediated, angiotensin-independent profibrotic effects. We therefore investigated whether PRR activation leads to the limited anti-fibrotic effects of AT1R blockade on DN, and whether PRR inhibition might ameliorate progression of DN. Methods: To address the issue, the expression of RAS components was tested in different stages of streptozotocin (STZ)-induced diabetic rats (6, 12, and 24 weeks) and 6-week AT1R blockade (losartan) treated diabetic rats. Using the blocker for PRR, the handle region peptide (HRP) of prorenin, the effects of PRR on high glucose or Ang II-induced proliferative and profibrotic actions were evaluated by measurement of cell proliferation, matrix metalloproteinase-2 (MMP-2) activity, activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and transforming growth factor-β1 (TGF-β1) expression in rat mesangial cells (MCs). Results: PRR was downregulated in the kidneys of different stages of diabetic rats (6, 12, and 24 weeks). Moreover, 6-week losartan treatment further suppressed PRR expression via upregulating AT2R, and ameliorated diabetic renal injury. HRP inhibited high glucose and Ang II-induced proliferative and profibrotic effects in MCs through suppressing TGF-β1 expression and activating MMP-2. Meanwhile, HRP enhanced losartan's anti-fibrotic effects through further inhibiting phosphorylation of ERK1/2 and TGF-β1 expression. Moreover, the inhibitive effect of HRP on Ang II-induced TGF-β1 expression depended on the regulation of PRR expression by AT2R. Conclusions: Our findings suggest that inhibition of PRR contributes to renoprotection against diabetic nephropathy by AT1R blockade.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 23%
Student > Bachelor 3 23%
Lecturer 1 8%
Other 1 8%
Student > Doctoral Student 1 8%
Other 0 0%
Unknown 4 31%
Readers by discipline Count As %
Medicine and Dentistry 4 31%
Biochemistry, Genetics and Molecular Biology 2 15%
Immunology and Microbiology 2 15%
Chemical Engineering 1 8%
Agricultural and Biological Sciences 1 8%
Other 0 0%
Unknown 3 23%
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 09 October 2017.
All research outputs
#20,449,496
of 23,005,189 outputs
Outputs from Frontiers in Physiology
#9,475
of 13,760 outputs
Outputs of similar age
#282,128
of 323,390 outputs
Outputs of similar age from Frontiers in Physiology
#228
of 321 outputs
Altmetric has tracked 23,005,189 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,760 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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