Abstract
BackgroundEndothelial-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.MethodsMale 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 α-SMA. CD31, α-SMA and Snail mRNA were detected by RT-PCR. Protein expression was detected by western blot.ResultsRenal 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+/α-SMA+ cells increased, which indicated EndoMT. However, the percentage of CD31+/α-SMA+ cells were reduced in the netrin-1-treated 5/6 Nx rats, which indicates netrin-1-induced blocking of EndoMT.ConclusionFrom 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.
Highlights
Endothelial-to-mesenchymal transition (EndoMT) is a crucial event during kidney interstitial fibrosis and it is believed to be inhibited by netrin-1
EndoMT was first investigated as a critical process in heart development, and studies have shown that EndoMT contributes to the development of diabetic renal interstitial fibrosis, diabetic nephropathy, and cardiac fibrosis, which indicates a relationship between EndoMT and fibrosis [5,6,7]
In the present study, using netrin-1-expressing adenovirus, we have provided evidence for the role of netrin-1 in EndoMT that occurs in chronic kidney disease (CKD) by showing that netrin-1 can prevent renal dysfunction and attenuate the process of EndoMT in the 5/6 5/ 6nephrectomized (Nx) rat model
Summary
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. Endothelial-mesenchymal transition (EndoMT) has emerged as another potentially important mechanism that is involved in both the developmental and pathological processes of kidney interstitial fibrosis. Fibroblasts are likely to be of endothelial origin, so it is possible that EndoMT contributes substantially to the accumulation of fibroblasts in the development and progression of renal. EndoMT was first investigated as a critical process in heart development, and studies have shown that EndoMT contributes to the development of diabetic renal interstitial fibrosis, diabetic nephropathy, and cardiac fibrosis, which indicates a relationship between EndoMT and fibrosis [5,6,7]. The mechanism via which EndoMT affects fibrosis remains largely unknown
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