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Eur J Pharmacol. 2019 Jun 15;853:289-298. doi: 10.1016/j.ejphar.2019.04.012. Epub 2019 Apr 10.

C1q/TNF-related protein-9 attenuates retinal inflammation and protects blood-retinal barrier in db/db mice.

European journal of pharmacology

Wei Li, Ning Ma, Ming-Xin Liu, Bing-Jie Ye, Yan-Jun Li, Hong-Yao Hu, Yan-Hong Tang

Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
  2. Eye Center, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
  3. Department of Interventional Radiology, Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
  4. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China. Electronic address: [email protected].

PMID: 30978318 DOI: 10.1016/j.ejphar.2019.04.012

Abstract

C1q/TNF-related protein-9(CTRP9) is an adipose cytokine, a closest adiponectin paralog, which has anti-inflammatory, antioxidant, vasodilation and anti-atherosclerosis effects. In addition, it can increase insulin sensitivity, decrease blood glucose level and inhibit the apoptosis of endothelial cells. However, it remains unclear whether CTRP9 has beneficial effects on diabetic retinopathy (DR). An adenoviral vector expressing CTRP9 was intravenously injected into db/db mice, aged 12 weeks, at day 15 post injection, and the process was repeated. The transfection efficiency of CTRP9 was assessed by enzyme linked immunosorbent assay. We used RT-PCR, immunofluorescence, and Western blot to determine proinflammatory cytokines, adhesion molecules and tight-junction proteins. The breakdown of blood-retinal barrier (BRB) was evaluated using Evans blue and retinal staining. CTRP9 suppresses the expression of interleukin-1 beta, tumor necrosis factor-alpha, monocyte chemotactic protein-1 and adhesion molecules in the retina of db/db mice. CTRP9 can balance the expression of pigment epithelium-derived factor and vascular endothelial growth factor. CTRP9 can also inhibit the activation of nuclear factor Kappa B in the retina of db/db mouse. In addition, CTRP9 can prevent the breakdown of BRB and downregulation of tight-junction proteins in the retina of db/db mice. Evans blue assay revealed the breakdown of BRB and vascular leakage in the retinas of diabetic mice. CTRP9 can both qualitatively and quantitatively alleviate the vascular leakage in the early stage of diabetic retinas. CTRP9 can inhibit the inflammation of diabetic retinopathy and protect blood-retinal barrier via decreasing proinflammatory cytokines and preventing the downregulation of tight-junction proteins.

Copyright © 2019 Elsevier B.V. All rights reserved.

Keywords: Blood–retinal barrier; CTRP9; Db/db mice; Diabetic retinopathy

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