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2016 ; 17
(1
): 47
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Netrin-1 attenuates the progression of renal dysfunction by blocking
endothelial-to-mesenchymal transition in the 5/6 nephrectomy rat model
#MMPMID27176224
Bai J
; Hao J
; Zhang X
; Cui H
; Han J
; Cao N
BMC Nephrol
2016[May]; 17
(1
): 47
PMID27176224
show ga
BACKGROUND: Endothelial-to-mesenchymal transition (EndoMT) is a crucial event
during kidney interstitial fibrosis and it is believed to be inhibited by
netrin-1. Our aim was to determine the influence of netrin-1 on renal EndoMT in
chronic kidney disease by studying its effect in 5/6 nephrectomized (Nx) rats.
METHODS: Male Sprague-Dawley rats were divided into three groups (10 rats/group):
sham-operated rats treated with control adenovirus; 5/6 Nx rats treated with
control adenovirus; and 5/6 Nx rats treated with recombinant adenovirus
expressing the netrin-1 gene (Ad-netrin-1). Rats were sacrificed 13 weeks after
surgery. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels were
measured regularly after surgery. After the rats were sacrificed, pathological
changes in renal tissues were analyzed histologically. Immunofluorescence was
performed to evaluate the co-expression of CD31 and ?-SMA. CD31, ?-SMA and Snail
mRNA were detected by RT-PCR. Protein expression was detected by western blot.
RESULTS: Renal function and histopathological damage were significantly improved
in Ad-netrin-1-treated 5/6 Nx rats. In the sham and control-treated 5/6 Nx rats,
the percentage of CD31(+)/?-SMA(+) cells increased, which indicated EndoMT.
However, the percentage of CD31(+)/?-SMA(+) cells were reduced in the
netrin-1-treated 5/6 Nx rats, which indicates netrin-1-induced blocking of
EndoMT. CONCLUSION: From the results, it seems that netrin-1 attenuates the
progression of renal dysfunction by inhibiting EndoMT in 5/6 Nx rats. Netrin-1
can therefore be considered as a potential therapeutic agent for the treatment of
renal fibrosis.