Basic regulatory effects and clinical value of metalloproteinase-14 and extracellular matrix metalloproteinase inducer in diabetic retinopathy

This study examined the basic regulatory effects and clinical value of metalloproteinase-14 and extracellular matrix metalloproteinase inducer in diabetic retinopathy. Seventy-four patients with diabetic retinopathy (study group/diabetic retinopathy (DR) group) and 48 healthy people (control group) were included in this study. Venous blood of subjects in the two groups was collected and the plasma levels of EMMPRIN, MMP-14, VEGF, and MMP-9 were determined by enzyme-linked immunosorbent assay. The value of applying plasma EMMPRIN and MMP-14 for predicting the prognosis of DR was evaluated using a receiver operating characteristic (ROC) curve with a 1-year follow-up. Human umbilical vein endothelial cells (HUVECs) were cultured in high-glucose conditions. EMMPRIN and MMP-14 mRNA levels were determined by RT-qPCR, EMMPRIN and MMP-14 protein levels were determined by Western blotting, apoptosis was determined by flow cytometry, and the level of angiogenesis was recorded. The levels of EMMPRIN and MMP-14 in the DR group were increased compared with those in the control group. Plasma EMMPRIN was positively correlated with plasma MMP-9 and plasma VEGF, and its area under the curve (AUC) for predicting 1-year adverse outcome of DR was 0.676. Plasma MMP-14 was also positively correlated with plasma MMP-9 and plasma VEGF, and its AUC for predicting 1-year adverse outcome of DR was 0.650. EMMPRIN and MMP-14 were upregulated in high-glucose-induced HUVECs. Downregulation of EMMPRIN resulted in downregulation of MMP-14, and downregulation of MMP-14 and EMMPRIN resulted in decreased apoptosis and angiogenesis of HUVECs. These findings suggest that EMMPRIN promotes endothelial cell apoptosis and angiogenesis in DR through MMP-14, and that plasma EMMPRIN and MMP-14 can help predict the short-term prognosis of DR.

The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse

Summary Objective This study investigated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse in rat molars. Materials and methods Thirty Wistar rats (6 weeks old) underwent orthodontic tooth movement (OTM) of the left first maxillary molar for 21 days, followed by removal of the force device. The contralateral maxillary molar served as a control with no mechanical force stimuli. Animals were sacrificed at 0, 1, 3, 7, and 14 days of relapse after force withdrawal. Tooth relapse and alveolar bone parameters were measured using microcomputed tomography (micro-CT). Maxilla sections were obtained for haematoxylin and eosin (HE), immunohistochemical staining [EMMPRIN, nuclear factor kappa B ligand (RANKL) and vascular endothelial growth factor (VEGF)] and tartrate-resistant acid phosphatase (TRAP). Correlation analyses were then performed. Results After force removal, nearly 79.88% of the total relapse occurred within the initial 3 days. The number of osteoclasts clearly increased while the alveolar bone density decreased on the pressure side on Day 3 of relapse. Moreover, the EMMPRIN expression level significantly increased on Day 1, peaked up on Day 3 and decreased on Days 7 and 14. Statistically, a strong positive correlation was found between EMMRPIN expression and the osteoclast number and RANKL and VEGF expression. Conclusion EMMPRIN was highly expressed on the pressure side during the orthodontic tooth relapse, which could be involved in osteoclastogenesis and alveolar bone resorption in association with RANKL and VEGF expression.

Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide

Lack of endothelial nitric oxide causes endothelial dysfunction and circulating monocyte infiltration, contributing to systemic atheroma plaque formation in arterial territories. Among the different inflammatory products, macrophage-derived foam cells and smooth muscle cells synthesize matrix metalloproteinases (MMPs), playing a pivotal role in early plaque formation and enlargement. We found increased levels of MMP-9 and MMP-13 in human endarterectomies with advanced atherosclerosis, together with significant amounts of extracellular matrix (ECM) metalloproteinase inducer EMMPRIN. To test whether the absence of NO may aggravate atherosclerosis through EMMPRIN activation, double NOS3/apoE knockout (KO) mice expressed high levels of EMMPRIN in carotid plaques, suggesting that targeting extracellular matrix degradation may represent a new mechanism by which endothelial NO prevents atherosclerosis. Based on our previous experience, by using gadolinium-enriched paramagnetic fluorescence micellar nanoparticles conjugated with AP9 (NAP9), an EMMPRIN-specific binding peptide, magnetic resonance sequences allowed non-invasive visualization of carotid EMMPRIN in NOS3/apoE over apoE control mice, in which atheroma plaques were significantly reduced. Taken together, these results point to EMMPRIN as a new therapeutic target of NO-mediated protection against atherosclerosis, and NAP9 as a non-invasive molecular tool to target atherosclerosis.