In:
Experimental Biology and Medicine, SAGE Publications, Vol. 237, No. 8 ( 2012-08), p. 894-902
Abstract:
Endothelin A receptor (ETaR) is a key molecule involved in a variety of biological events such as vessel contraction and inflammatory response in ischemia-reperfusion (I/R) injury. RNA interference using short hairpin RNA (shRNA) is a powerful tool to silence gene expression. Here, the effect of ETaR shRNA on I/R injury in rats was studied. A more effective shRNA sequence out of two constructed into plasmid vectors was selected using the A-10 cell line, and was then applied to a rat model. Twenty-eight male Sprague-Dawley rats were randomized into four groups: Sham, shRNA, vector and phosphate-buffered saline (PBS). Renal I/R injury was induced by clamping the left renal pedicle for one hour followed by reperfusion for 24 h. ETaR shRNA (100 μg) plasmid was administered by renal vein injection 48 h before clamping. The expression of both ETaR mRNA and protein was lowered by ETaR shRNA treatment compared with that in the vector and PBS groups; serum creatinine and blood urea nitrogen were significantly decreased; the semi-quantitative score of renal structural damage was improved; the mRNA level of endothelin 1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), macrophage inflammatory protein 2 (MIP-2) and monocyte chemoattractant protein 1 (MCP-1) was reduced, but nitric oxide (NO) production in kidney tissues was increased ( P 〈 0.05). In conclusion, ETaR shRNA partially silenced ETaR expression in I/R injury kidneys, reduced the mRNA level of ET-1, inflammatory mediators including TNF-α, IL-6, MIP-2 and MCP-1, increased NO production, and ultimately improved renal function and structure.
Type of Medium:
Online Resource
ISSN:
1535-3702
,
1535-3699
DOI:
10.1258/ebm.2012.011368
Language:
English
Publisher:
SAGE Publications
Publication Date:
2012
detail.hit.zdb_id:
2020856-X
SSG:
12
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