383-P: A Novel Role of AQP1 in Angiogenesis of Diabetic Kidney Disease

Introduction&Objective: Angiogenesis is the formation of new blood vessels from pre-existing vasculature. Glomerular endothelial dysfunction and neoangiogenesis have long been implicated in the pathogenesis of diabetic kidney disease (DKD). Aquaporin 1 (AQP1) is a glycoprotein responsible for water passive transport quickly across biological membrane and involved in the angiogenesis. However, AQP1^,s role in the angiogenesis of DKD has been unclear.

Methods: Db/db mice and streptozotocin-induced diabetic mice with high-fat diet (STZ mice) were used. The expression of AQP1, endothelial markers CD31 and angiogenic factors (VEGF and VEGFR ) was measured by Real-time quantitative PCR (Q-PCR), immunofluorescence (IF), immunohistochemical staining (IHC) and Western blot (WB) analysis. Furthermore, the role of AQP1 in adhesion, invasion and angiogenesis of mouse glomerular vascular endothelial cells (MGECs) was determined by transfection of adenovirus encoding a mouse AQP1.

Results: AQP1, VEGF and VEGFR was elevated expression in the diabetic kidneys of db/db mice and STZ mice by Q-PCR. Specifically, overexpression of AQP1 gene increased adhesion, invasion and angiogenesis of MGECs cells. Furthermore, AQP1 induced the increase of VEGF and VEGFR by IF, Q-PCR and WB as well as CD31, endothelial markers, in MGECs cells.

Conclusion: Our study provides new insights into AQP1 as a potential novel pathogenic mediator of diabetic glomerular neoangiogenesis and a risk factor in DKD progression.