RP105 alleviates myocardial ischemia reperfusion injury via inhibiting TLR4/TRIF signaling pathways

Yang,Jun; Yang,Chaojun; Yang,Jian; Ding,Jiawang; Li,Xinxin; Yu,Qinqin; Guo,Xin; Fan,Zhixing; Wang,Huibo

doi:10.3892/ijmm.2018.3538

RP105 alleviates myocardial ischemia reperfusion injury via inhibiting TLR4/TRIF signaling pathways

Authors:
- Jun Yang
- Chaojun Yang
- Jian Yang
- Jiawang Ding
- Xinxin Li
- Qinqin Yu
- Xin Guo
- Zhixing Fan
- Huibo Wang
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Affiliations: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei 443000, P.R. China, Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, Hubei 443000, P.R. China
Published online on: March 6, 2018 https://doi.org/10.3892/ijmm.2018.3538
Pages: 3287-3295
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Toll-like receptor 4 (TLR4) signal pathway- induced inflammation is considered to be a crucial link to myocardial ischemia reperfusion injury (MIRI). Our previous study proved that radioprotective 105 kDa protein (RP105), a negative regulator of TLR4, performed a protective role in MIRI by anti-apoptosis approach. However, the mechanism of RP105 cardioprotection of anti-inflammation is still unclear. This study aimed to explore the underlying mechanism of RP105 anti-inflammation effect in MIRI. We established a rat model of MIRI induced by ligation of the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. Animals were pre-infected with Ad-EGFP-RP105, Ad-EGFP or saline at the apex of the heart. All rats were sacrificed to collect blood samples and myocardial tissue and assessed by immunofluorescence, blood biochemical analysis, Evans blue/triphenyltetrazolium chloride (TTC), hematoxylin and eosin (H&E) staining, enzyme-linked immuno sorbent assay (ELISA), western blot analysis, quantitative PCR and electrophoretic mobility shift assay (EMSA). RP105 overexpression with adenovirus vectors reduced serum myocardial enzyme (CK-MB and LDH) activities, decreased myocardial infarct size, mitigated inflammatory factors interferon-β and tumor necrosis factor-α during MIRI. We also found that Ad-RP105 group exerted distinct repression of TLR4/TRIF signal pathway related proteins and mRNAs (TRIF, TBK-1, IRF3 and p-IRF3) with a low transcriptional activity of IRF3. These findings first expounded that RP105 could alleviate the ischemia reperfusion induced inflammatory status in heart via inhibiting TLR4/TRIF signaling pathway and provided a theoretical foundation of RP105 gene in MIRI.

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