Changes of podocyte p130Cas in diabetic conditions

Title
Changes of podocyte p130Cas in diabetic conditions
Author(s)
한기동하태선[하태선]최지영[최지영]박희영[박희영]
Keywords
GLOMERULAR EPITHELIAL-CELLS; FOCAL ADHESION KINASE; TYROSINE PHOSPHORYLATION; V-CRK; P130(CAS); PROTEIN; SRC; NEPHROPATHY; INHIBITION; EXPRESSION
Issue Date
201310
Publisher
WICHTIG EDITORE
Citation
JOURNAL OF NEPHROLOGY, v.26, no.5, pp.870 - 876
Abstract
Background; Proteinuria results from increased glomerular permeability and is associated with retraction and effacement of the highly specialized interdigitating podocyte foot processes. In podocytes (glomerular epithelial cells [GECs]), p130Cas localizes diffusely to the cytoplasm and connects focal adhesion proteins and kinases to the glomerular basement membrane and adapter proteins of slit diaphragm insertion sites. Methods: To investigate whether high-glucose (HG) and advanced glycosylation end products (AGEs) induce quantitative and distributional changes of podocyte p130Cas protein, a docking protein connecting F-actin fibers to the glomerular basement membrane and adapter proteins, we cultured rat GECs (r-GECs) and mouse GECs (m-GECs) under (i) normal glucose (5 mM = control), (ii) HG (30 mM), (iii) AGE-added or (iv) HG plus AGE-added conditions. We also prepared streptozotocin-induced diabetic renal tissues. Results: We found that p130Cas stainings were located in peripheral cytoplasm of r-GECs and m-GECs as dots in linear alignment, partially colocalized with actinbinding proteins such as synaptopodin and lx-actinin, and locally connected to the ends of actin filaments. In diabetic conditions, the intensities of p130Cas stainings were diminished in more pathological HG plus AGE-added condition of r-GECs and m-GECs and in chronic diabetic renal tissues. p130Cas protein was decreased significantly by HG, AGE and HG plus AGE in both cells compared with normal glucose or osmotic control conditions. p130Cas mRNA expression levels were also suppressed similarly in diabetic conditions. Conclusion; We suggest that diabetic conditions modulate the quantitative and distributional changes of podocyte p130Cas and therefore affect the filtration function of podocytes.
URI
http://hdl.handle.net/YU.REPOSITORY/28809http://dx.doi.org/10.5301/jn.5000261
ISSN
1121-8428
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