title: Extracellular matrix metalloproteinase inducer (EMMPRIN) is a potential biomarker of angiogenesis in proliferative diabetic retinopathy.
abstract: OBJECTIVE
  Extracellular matrix metalloproteinase inducer (EMMPRIN) promotes angiogenesis through matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) production. We investigated the expression levels of EMMPRIN and correlated these levels with VEGF, MMP-1 and MMP-9 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of EMMPRIN in the retinas of diabetic rats and the effect of EMMPRIN on the induction of angiogenesis regulatory factors in human retinal microvascular endothelial cells (HRMECs).
  
  
  METHODS
  Vitreous samples from 40 PDR and 19 non-diabetic patients, epiretinal membranes from 12 patients with PDR, retinas of rats and HRMECs were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, Western blot analysis, zymography analysis and RT-PCR.
  
  
  RESULTS
  We showed a significant increase in the expression of EMMPRIN, VEGF, MMP-1 and MMP-9 in vitreous samples from PDR patients compared with non-diabetic controls (p < 0.0001; p = 0.001; p = 0.009; p < 0.0001, respectively). Significant positive correlations were found between the levels of EMMPRIN and the levels of VEGF (r = 0.38; p = 0.003), MMP-1 (r = 0.36; p = 0.005) and MMP-9 (r = 0.46; p = 0.003). In epiretinal membranes, EMMPRIN was expressed in vascular endothelial cells and stromal cells. Significant increase of EMMPRIN mRNA was detected in rat retinas after induction of diabetes. EMMPRIN induced hypoxia-inducible factor-1α, VEGF and MMP-1 expression in HRMEC.
  
  
  CONCLUSIONS
  These results suggest that EMMPRIN/MMPs/VEGF pathway is involved in PDR angiogenesis.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.|Dr. Nasser Al-Rashid Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ajmal
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Kaiser
authors.initials: K
authors.lastname: Alam
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad Mairaj
authors.initials: MM
authors.lastname: Siddiquei
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.affiliation: Laboratory of Histochemistry and Cytochemistry, University of Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Gert De
authors.initials: G
authors.lastname: Hertogh
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000818:Animals; D051926:Basigin / Q000096:biosynthesis / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D012313:RNA / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014822:Vitreous Body / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D051926:Basigin; D012313:RNA
keywords: 
  EMMPRIN
  ; angiogenesis; matrix metalloproteinases; proliferative diabetic retinopathy; vascular endothelial growth factor