Eucalyptol Inhibits Advanced Glycation End Products-Induced Disruption of Podocyte Slit Junctions by Suppressing Rage-Erk-C-Myc Signaling Pathway.
Mol Nutr Food Res. 2018 10 ;62(19):e1800302. Epub 2018 Aug 7. PMID: 29987888
Dong Yeon Kim
SCOPE: The maintenance of interpodocyte slit diaphragm is critical in the sieving function of glomerular filtration barrier. Eucalyptol is a natural constituent in aromatic plants with antioxidant properties. This study investigates whether and how eucalyptol inhibits podocyte slit diaphragm malfunction in glucose-exposed podocytes and diabetic mouse kidneys.
METHODS AND RESULTS: Podocytes were incubated in media containing 33 mm glucose with 1-20 μm eucalyptol. The in vivo model employed db/db mice orally administrated with 10 mg kgeucalyptol. Nontoxic eucalyptol enhanced podocyte expression of nephrin, podocin, FAT-1, CD2AP, andα-actinin-4 diminished by glucose. Oral administration of eucalyptol augmented the induction of the slit diaphragm proteins, α-actinin-4, and integrin β1 in diabetic kidneys, and ameliorated glomerular fibrosis and foot process effacement. Eucalyptol counteracted the receptor of advanced glycation end products (RAGE) induction in podocytes with glucose or AGE-BSA, and elevated the reduction of the slit diaphragm proteins by AGE-BSA. Eucalyptol attenuated the RAGE induction and AGE accumulation in diabetic kidneys. The blockade of ERK-c-Myc signaling enhanced the nephrin and CD2AP expressiondownregulated in AGE-exposed podocytes. These results indicate that eucalyptol blocked glucose-induced AGE-RAGE axis and podocyte injury through disturbing RAGE-ERK-c-Myc signaling.
CONCLUSION: Eucalyptol may be a potent agent antagonizing diabetes-associated malformation of interpodocyte slit junction and podocyte actin cytoskeleton.