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Sampathkumar Rangasamy, Joann Maestas, Arup Das, Paul McGuire; Sphingosine-1-phosphate (S1P) Regulation of Pericyte/Endothelial Interaction: Implications In Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3571. doi: https://doi.org/.
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Endothelial-pericyte interactions are important for normal function of the microcirculation. Pericyte loss and subsequent alteration of the blood-retinal barrier is the hallmark of diabetic macular edema (DME). In this study, we investigated the role of N-cadherin and s1p, in mediating the interaction between endothelial cells and pericytes and its alteration in response to hyperglycemia
Diabetes was induced in Sprague-Dawley rats using streptozotocin and human retinal microvascular endothelial cells (HRECs) and pericytes were exposed to low and high glucose (30.5 mM). The expression of p120 and N-Cadherin was examined using western blot and RT PCR techniques. The role of N-cadherin/s1p in mediating endothelial/pericyte interactions and endothelial barrier function was examined by immunofluroescence and electric cell substrate impedance sensing (ECIS)
N-cadherin promotes the attachment of pericytes to endothelial monolayer and is not involved directly in inter-endothelial interactions. Pericytes through the secretion of s1p mediates the expression of N-cadherin in endothelial cells and increases endothelial barrier properties. Further, through the receptor antagonist studies, we identified that S1P increases endothelial barrier integrity through its interaction with S1PR1. High glucose reduced the level of N-cadherin and p120 protein in human retinal microvascular endothelial cells and pericytes. In addition, treatment with Ang-2 leads to loss of N-cadherin in both pericytes and endothelial cells
N-cadherin promotes the attachment of pericytes to endothelial cells. S1P produced by pericytes increases N-cadherin expression and regulates endothelial barrier function. Hyperglycemia or Ang-2 reduced N-cadherin expression and may play a role in the alteration of retinal barrier function through the loss of pericytes. Study of the role of N-cadherin and the S1P pathway in diabetes could potentially lead to the identification of a new molecular target for treating diabetic retinopathy
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