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2016 ; 94
(2
): 207-18
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Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced
diabetic nephropathy
#MMPMID26407577
Ding D
; Du Y
; Qiu Z
; Yan S
; Chen F
; Wang M
; Yang S
; Zhou Y
; Hu X
; Deng Y
; Wang S
; Wang L
; Zhang H
; Wu H
; Yu X
; Zhou Z
; Liao Y
; Chen X
J Mol Med (Berl)
2016[Feb]; 94
(2
): 207-18
PMID26407577
show ga
Recently, our group has developed a therapeutic hypertensive vaccine against
angiotensin (Ang) II type 1 receptor (AT1R) named ATRQ?-001. To explore its
potential effectiveness on streptozotocin-induced diabetic nephropathy, male
Sprague Dawley rats were randomly divided into two groups: a control and a
diabetic model. After 1 week, the diabetic rats were divided into four subgroups
(each with 15 rats) for 14-week treatments with saline, olmesartan, ATRQ?-001,
and Q? virus-like particle (VLP), respectively. In addition to lower blood
pressure, ATRQ?-001 vaccination ameliorated biochemical parameter changes of
renal dysfunction, mesangial expansion, and fibrosis through inhibiting oxidative
stress, macrophage infiltration, and proinflammatory factor expression.
Furthermore, ATRQ?-001 vaccination suppressed renal Ang II-AT1R activation and
abrogated the downregulation of angiotensin-converting enzyme 2-Ang (1-7),
similar to olmesartan treatment, while no obvious feedback activation of
circulating or local renin-angiotensin system (RAS) was only observed in vaccine
group. In rat mesangial cells, the anti-ATR-001 antibody inhibited high
glucose-induced transforming growth factor-?1 (TGF)-?1/Smad3 signal pathway.
Additionally, no significant immune-mediated damage was detected in vaccinated
animals. In conclusion, the ATRQ?-001 vaccine ameliorated streptozotocin-induced
diabetic renal injury via modulating two RAS axes and inhibiting TGF-?1/Smad3
signal pathway, providing a novel, safe, and promising method to treat diabetic
nephropathy. KEY MESSAGES: Overactivation of RAS plays a crucial role in the
development of the DN. Our aim was to verify the effectiveness of ATRQ?-001
vaccine in STZ-induced DN. The ATRQ?-001 modulated two RAS axes and inhibited
TGF-?1/Smad3 signal pathway. The vaccine therapy may provide a novel, safe, and
promising method to treat DN.
|Angiotensin II/blood
[MESH]
|Animals
[MESH]
|Biomarkers
[MESH]
|Blood Chemical Analysis
[MESH]
|Blood Pressure
[MESH]
|Diabetes Mellitus, Experimental
[MESH]
|Diabetic Nephropathies/*etiology/metabolism/pathology/*prevention & control
[MESH]
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