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Y. Sassa, S.L. Rook, A.C. Clermont, B. Gao, E.P. Feener, L.P. Aiello; Regulation of Dickkopf Protein 3 in Retinal Cells and Diabetic Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):964.
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© ARVO (1962-2015); The Authors (2016-present)
Using proteomic analyses, we recently identified the Wnt signaling antagonist Dickkopf protein 3 (DKK3) as being reduced in the vitreous of patients with PDR. DKK–3 has tumor suppressor, apoptosis and anti–proliferative activities and is involved in cellular migration and differentiation. We examined the expression and regulation of DKK3 in retina and cultured retinal cells.
DKK3 mRNA expression in bovine retinal capillary endothelial cells (REC), pericytes (RPC) and pigment epithelial cells (RPE) were assessed by Northern blot and RT–PCR analysis. Retinal DKK1–3 expression was evaluated in control and streptozotocin–induced diabetic mice (C57/BL6) by RT–PCR.
DKK3 gene expression was detected in all cultured retinal cells examined. Expression was 10.3– and 3.8–fold higher in RPC and RPE, respectively, than in REC. DKK3 expression was increased by cellular confluency 1.4– and 2.3–fold in REC and RPE, respectively. High glucose exposure (22mM) for 5 days decreased DKK3 gene expression in RPC 24% (p=0.039) as compared with normal glucose (5.5mM) of equal osmolarity. Insulin (100nM) increased DKK3 gene expression in RPC in a time and dose–dependent manner (180%+30% at 4 hours), an effect maintained at least 10 hours. DKK2&3, but not DKK1, were detected in normal mouse retina. DKK–3 gene expression decreased in mouse retina after 8 weeks of diabetes by 24% (p=0.017) as compared to nondiabetic retina.
DKK3 expression is decreased in diabetic retina and is regulated by cell confluency, glucose concentration, and insulin in retinal cells in culture. These findings suggest a possible regulatory role of DKK3 in mediating retinal complications of diabetes.
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