Diabetic conditions downregulate the expression of CD2AP in podocytes via PI3-K/Akt signalling

• Published in: Diabetes/metabolism research and reviews Vol. 31; no. 1; pp. 50 - 60
• Main Authors: Ha, Tae-Sun, Hong, Eun-Jeong, Han, Gi-Dong
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2015; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; advanced glycosylation end products; Animals; CD2AP; Cells, Cultured; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; diabetic nephropathy; Down-Regulation - drug effects; Down-Regulation - genetics; glomerular epithelial cells; Glucose - pharmacology; Mice; Oncogene Protein v-akt - metabolism; Oncogene Protein v-akt - physiology; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol 3-Kinases - physiology; PI3-K/Akt signalling; podocyte; Podocytes - drug effects; Podocytes - metabolism; Podocytes - pathology; Rats; Signal Transduction - drug effects; Signal Transduction - genetics; Streptozocin; PI3-K/Akt signalling; glomerular epithelial cells; advanced glycosylation end products; diabetic nephropathy; podocyte; CD2AP
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.2562

Background Proteinuria is typically accompanied by structural and compositional changes of the foot processes and of the slit diaphragms between podocytes. CD2‐associated protein (CD2AP) in podocytes serves as an adaptor protein binding to nephrin and podocin, anchoring these slit diaphragm proteins to actin filaments of podocyte cytoskeleton and sending signals inward or outward. Methods In the present study, we prepared streptozotocin‐induced diabetic renal tissues and cultured podocytes in diabetic conditions to investigate podocyte phenotypical changes, including quantitative and distributional changes of CD2AP protein and search for the signalling mechanisms in diabetic conditions. We prepared cultured rat glomerular epithelial cells and mouse podocytes to study how high glucose and advanced glycosylation end products (AGE) induce phenotypical changes of cultured podocyte, under (1) normal glucose (5 mM, = control), (2) high glucose (30 mM), (3) AGE‐added or (4) high glucose plus AGE‐added conditions. Results According to diabetic duration, density of CD2AP in renal tissue of experimental diabetic nephropathy became conglomerulated and diminished. In cultured podocytes, CD2AP co‐localized with nephrin and zonula occludens‐1 by confocal imaging. High glucose and high glucose plus AGE induced the relocalization and concentration of CD2AP at internal cytoplasmic and perinuclear areas of podocytes. High glucose plus AGE‐added condition also decreased CD2AP protein amount and its mRNA expression compared with normal glucose or osmotic control conditions. In addition, LY294002, a phosphoinositide 3‐kinase inhibitor, prevented the quantitative and distributional changes of CD2AP induced by high glucose and AGE. Conclusions These findings suggest that diabetic conditions induce the phenotypical changes of podocyte CD2AP possibly via phosphoinositide 3‐kinase/Akt signalling. Copyright © 2014 John Wiley & Sons, Ltd.