CTRP3 is a novel biomarker for diabetic retinopathy and inhibits HGHL-induced VCAM-1 expression in an AMPK-dependent manner

Zheyi Yan; Jianli Zhao; Lu Gan; Yanqing Zhang; Rui Guo; Xiaoming Cao; Wayne Bond Lau; Xin Ma; Yajing Wang

doi:10.1371/journal.pone.0178253

CTRP3 is a novel biomarker for diabetic retinopathy and inhibits HGHL-induced VCAM-1 expression in an AMPK-dependent manner

PLoS One. 2017 Jun 20;12(6):e0178253. doi: 10.1371/journal.pone.0178253. eCollection 2017.

Authors

Zheyi Yan^{1

2}, Jianli Zhao^{2

3}, Lu Gan^{2

4}, Yanqing Zhang^{2

3}, Rui Guo^{2

4}, Xiaoming Cao⁵, Wayne Bond Lau², Xin Ma^{2

4}, Yajing Wang^{2

4}

Affiliations

¹ Department of Ophthalmology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
² Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States of America.
³ Department of Anesthesiology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
⁴ Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, China.
⁵ Department of Orthopedics, The Second Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.

Abstract

Objectives: Diabetic retinopathy (DR) is a severe complication of chronic diabetes. The C1q/TNF-related protein family (CTRPs) has been demonstrated to exert protective effects against obesity and atherosclerosis in animal studies. Heretofore, the association between circulating CTRPs and DR patients has been unexplored. In the current study, we attempt to define this association, as well as the effect of CTRPs upon DR pathophysiology.

Design: The present investigation is a case control study that enrolled control subjects and type 2 diabetes mellitus (T2DM) patients diagnosed with DR. Serum CTRPs and sVACM-1 were determined by ELISA.

Results: Serum CTRP3 and CTRP5 levels were markedly decreased in patients with T2DM compared to controls (p<0.05) and inversely associated with T2DM. Furthermore, mutivariate regression and ROC analysis revealed CTRP3 deficiency, not CTRP5, was associated with proliferative diabetic retinopathy (PDR). Spearman's rank correlation assay demonstrated an inverse association between CTRP3 and sVCAM-1. Finally, exogenous CTRP3 administration attenuated high glucose high lipid (HGHL)-induced VCAM-1 production in an AMPK-dependent manner in cultured human retinal microvascular endothelial cells (HRMECs).

Conclusion: CTRP3 may serve as a novel biomarker for DR severity. CTRP3 may represent a future novel therapeutic against DR, a common ocular complication of diabetes.

MeSH terms

AMP-Activated Protein Kinases / metabolism*
Biomarkers / metabolism*
Case-Control Studies
Cells, Cultured
Collagen / metabolism
Diabetes Mellitus, Type 2 / complications
Diabetic Retinopathy / diagnosis*
Diabetic Retinopathy / etiology
Diabetic Retinopathy / metabolism
Endothelium, Vascular / cytology
Endothelium, Vascular / drug effects
Endothelium, Vascular / metabolism
Female
Glucose / adverse effects*
Humans
Lipids / adverse effects*
Male
Middle Aged
Retinal Vessels / cytology
Retinal Vessels / drug effects
Retinal Vessels / metabolism
Tumor Necrosis Factors / metabolism*
Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

Biomarkers
C1QTNF3 protein, human
C1QTNF5 protein, human
Lipids
Tumor Necrosis Factors
Vascular Cell Adhesion Molecule-1
Collagen
AMP-Activated Protein Kinases
Glucose

Grants and funding

This work was supported by the following grants: Shanxi Animals’ Special Foundation 2015K01 (ZY. Yan); Shanxi Key Subjects Construction, Innovative Talents of Higher Learning Institutions of Shanxi, American Diabetes Association 1-14-BS-218, 1-17-IBS-297, Natural Science Foundation of China 81670278, 31322026 (Y. Wang); 81270185, 81470020 (J. Zhao); National Institutes of Health HL- 96686, HL-123404, and American Diabetes Association 1-15-BS-122 (X.L. Ma). The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript.