Matrix metalloproteinase-14 is a biomarker of angiogenic activity in proliferative diabetic retinopathy.

Abstract

Purpose:

Matrix metalloproteinase-14 (MMP-14) is a transmembrane MMP that plays a critical role in promoting angiogenesis. We investigated the expression levels of MMP-14 and correlated the levels with clinical disease activity and with the levels of the angiogenic factors vascular endothelial growth factor (VEGF) and MMP-9 in proliferative diabetic retinopathy (PDR). To reinforce the findings at the functional level, we examined the expression of MMP-14 in the retinas of diabetic rats.

Methods:

Vitreous samples from 34 patients with PDR and 18 nondiabetic patients and epiretinal membranes from 13 patients with PDR and the retinas of rats were studied with enzyme-linked immunosorbent assay, immunohistochemistry, western blotting, and real-time reverse transcription PCR (RT-PCR).

Results:

The MMP-14, VEGF, and MMP-9 levels were statistically significantly higher in the vitreous samples from patients with PDR than in the samples from the nondiabetic controls (p<0.001 for all comparisons). The MMP-14 levels in patients with PDR with active neovascularization were statistically significantly higher than those in patients with inactive PDR (p<0.001). There were statistically significant positive correlations between levels of MMP-14 and levels of VEGF (r = 0.3; p = 0.032) and MMP-9 (r = 0.54; p<0.001). In the epiretinal membranes, MMP-14 was expressed in vascular endothelial cells, leukocytes, and myofibroblasts. Statistically significant positive correlations were detected between the numbers of blood vessels expressing CD31 and the numbers of blood vessels (r = 0.74; p = 0.004) and stromal cells (r = 0.72; p = 0.005) expressing MMP-14. Statistically significant increases of MMP-14 mRNA and protein were detected in rat retinas after induction of diabetes.

Conclusions:

These results suggest that MMP-14 is involved in PDR angiogenesis.

• Authors: Ahmed M Abu El-Asrar, Ghulam Mohammad, Eef Allegaert, Ajmal Ahmad, Mohammad Mairaj Siddiquei, Kaiser Alam, Priscilla W Gikandi, Gert De Hertogh, Ghislain Opdenakker
• Journal: Molecular vision (Mol Vis) Vol. 24 Pg. 394-406 ( 2018) ISSN: 1090-0535 [Electronic] United States
• PMID: 29853773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• MMP9 protein, human
• Matrix Metalloproteinase 9
• MMP14 protein, human
• Matrix Metalloproteinase 14

Topics

• Adult
• Aged
• Animals
• Biomarkers (metabolism)
• Blood Vessels (metabolism, pathology)
• Case-Control Studies
• Diabetes Mellitus, Experimental (genetics, metabolism, pathology)
• Diabetic Retinopathy (genetics, metabolism, pathology)
• Endothelial Cells (metabolism, pathology)
• Female
• Gene Expression Regulation
• Humans
• Leukocytes (metabolism, pathology)
• Male
• Matrix Metalloproteinase 14 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Middle Aged
• Myofibroblasts (metabolism, pathology)
• Neovascularization, Pathologic (genetics, metabolism, pathology)
• Rats
• Retina (metabolism, pathology)
• Retinal Neovascularization (genetics, metabolism, pathology)
• Signal Transduction
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vitreous Body (blood supply, metabolism, pathology)