Eucalyptol Ameliorates Dysfunction of Actin Cytoskeleton Formation and Focal Adhesion Assembly in Glucose-Loaded Podocytes and Diabetic Kidney.

SCOPE Podocytes are a component of glomerular filtration barrier with interdigitating foot processes. The podocyte function depends on dynamics of actin cytoskeletal and focal adhesion crucial for foot process structure. This study investigated the renoprotective effects of eucalyptol on the F-actin cytoskeleton formation and focal adhesion assembly in glucose-loaded podocytes and diabetic kidneys. METHODS AND RESULTS Eucalyptol at 1-20 #x000B5;M reversed the reduction of cellular level of F-actin, ezrin, cortactin and Arp2/3 in 33 mM glucose-loaded mouse podocytes, and oral administration of 10 mg/kg eucalyptol elevated tissue levels of actin cytoskeletal proteins reduced in db/db mouse kidneys. Eucalyptol inhibited podocyte morphological changes, showing F-actin cytoskeleton formation in cortical regions and agminated F-actin along the cell periphery. Eucalyptol induced focal adhesion proteins of paxillin, vinculin, talin1, FAK and Src in glucose-exposed podocytes and diabetic kidneys. Additionally, GTP-binding Rac1, Cdc42, Rho A and ROCK were upregulated in glucose-stimulated podocytes and diabetic kidneys, which was attenuated by supplying eucalyptol. Rho A gene depletion partially diminished GSK3β induction of podocytes by glucose. CONCLUSION Eucalyptol ameliorated F-actin cytoskeleton formation and focal adhesion assembly through blockade of Rho signaling pathway entailing partial involvement of GSK3β, which may inhibit barrier dysfunction of podocytes and resultant proteinuria. This article is protected by copyright. All rights reserved.

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