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Extracellular matrix metalloproteinase inducer ( EMMPRIN ) is a potential biomarker of angiogenesis in proliferative diabetic retinopathy
Author(s) -
Abu ElAsrar Ahmed M.,
Ahmad Ajmal,
Alam Kaiser,
Siddiquei Mohammad Mairaj,
Mohammad Ghulam,
Hertogh Gert De,
Mousa Ahmed,
Opdenakker Ghislain
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.13284
Subject(s) - basigin , angiogenesis , matrix metalloproteinase , vascular endothelial growth factor , diabetic retinopathy , extracellular matrix , immunohistochemistry , western blot , metalloproteinase , medicine , zymography , vascular endothelial growth factor a , endocrinology , chemistry , diabetes mellitus , vegf receptors , biochemistry , gene
Purpose Extracellular matrix metalloproteinase inducer ( EMMPRIN ) promotes angiogenesis through matrix metalloproteinases ( MMP s) 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 ( HRMEC s). Methods Vitreous samples from 40 PDR and 19 non‐diabetic patients, epiretinal membranes from 12 patients with PDR , retinas of rats and HRMEC s 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‐1 α , VEGF and MMP ‐1 expression in HRMEC . Conclusions These results suggest that EMMPRIN / MMP s/ VEGF pathway is involved in PDR angiogenesis.