Ongoing efforts to remove pathological inflammatory stimuli are crucial for the protection of endothelial cells in diabetes. Nerve injury-induced protein 1 (Ninj1) is an adhesion molecule that not only contributes to inflammation but also regulates the apoptosis of endothelial cells. In the present study, Ninj1 was found highly expressed in endothelial cells in Type 2 diabetic mice and increased in high-glucose (HG) cultured HUVECs. Furthermore, we found that Ninj1 levels are up-regulated in endothelial cells in clinical specimens of diabetic patients when compared with nondiabetic tissues, indicating a biological correlation between Ninj1 and endothelial pathophysiology in diabetic condition. Functional blocking of Ninj1 promoted endothelial tube formation and eNOS phosphorylation in the HG condition. Additionally, blocking Ninj1 inhibited the activation of caspase-3 and increased the Bcl-2/Bax ratio, thus inhibiting HUVECs apoptosis induced by HG. HG-induced ROS overproduction, p38 MAPK and NF-κB activation, and the overexpression of VCAM-1, ICAM-1, MCP-1, and IL-6 genes were ameliorated after Ninj1 was blocked. Using the signaling pathway inhibitor LY294002, we found that Bcl-2 expression and eNOS phosphorylation after Ninj1 blockade were regulated via PI3K/Akt signaling pathway. The in vivo endothelial contents, α-SMA+PECAM-1+ vascular numbers, and blood perfusion in the hindlimb were markedly up-regulated after Ninj1 was blocked. According to our findings, functional blocking of Ninj1 shows protective effects on diabetic endothelial cells both in vitro and in vivo. Thus, we consider Ninj1 to be a potential therapeutic target for preventing endothelial dysfunction in diabetes mellitus.
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January 2018
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Oleic-acid-treated HepG2 cells immunostained for PGC-1α (PPARγ co-activator-1 α). In Clinical Science volume 132, issue 1, the results of work by Bernardi et al. include reporting that the protein TRAIL (TNF-related apoptosis inducing ligand) increases the expression of PGC-1α in HepG2 cells cultured with oleic acid. Overall, the article points to a potential therapeutic role for TRAIL against impaired glucose tolerance and non-alcoholic fatty liver disease; for details see pages 69–83.
Research Article|
January 19 2018
Functional blocking of Ninjurin1 as a strategy for protecting endothelial cells in diabetes mellitus
Xin Wang;
Xin Wang
*
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Jinbao Qin;
Jinbao Qin
*
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Xing Zhang;
Xing Zhang
*
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Zhiyou Peng;
Zhiyou Peng
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Kaichuang Ye;
Kaichuang Ye
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Xiaoyu Wu;
Xiaoyu Wu
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Xinrui Yang;
Xinrui Yang
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Huihua Shi;
Huihua Shi
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Zhen Zhao;
Zhen Zhao
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Xin Guo;
Xin Guo
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
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Xiaobing Liu;
Xiaobing Liu
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
2Vascular Center of Shanghai JiaoTong University, Shanghai, People’s Republic of China
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Minyi Yin;
Minyi Yin
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
2Vascular Center of Shanghai JiaoTong University, Shanghai, People’s Republic of China
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Xinwu Lu
1Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China
2Vascular Center of Shanghai JiaoTong University, Shanghai, People’s Republic of China
Correspondence: Xinwu Lu ([email protected])
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Publisher: Portland Press Ltd
Received:
August 08 2017
Revision Received:
December 10 2017
Accepted:
December 16 2017
Accepted Manuscript online:
December 20 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (2): 213–229.
Article history
Received:
August 08 2017
Revision Received:
December 10 2017
Accepted:
December 16 2017
Accepted Manuscript online:
December 20 2017
Citation
Xin Wang, Jinbao Qin, Xing Zhang, Zhiyou Peng, Kaichuang Ye, Xiaoyu Wu, Xinrui Yang, Huihua Shi, Zhen Zhao, Xin Guo, Xiaobing Liu, Minyi Yin, Xinwu Lu; Functional blocking of Ninjurin1 as a strategy for protecting endothelial cells in diabetes mellitus. Clin Sci (Lond) 31 January 2018; 132 (2): 213–229. doi: https://doi.org/10.1042/CS20171273
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