Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 62, Issue 19, Pages -Publisher
WILEY
DOI: 10.1002/mnfr.201800302
Keywords
advanced glycation end products; diabetic nephropathy; ERK signaling; eucalyptol; podocyte slit diaphragm
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Funding
- National Research Foundation of Korea (NRF) - Korea government (MEST) [2015R1A2A2A01006666]
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ScopeThe 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 resultsPodocytes were incubated in media containing 33mm glucose with 1-20m eucalyptol. The in vivo model employed db/db mice orally administrated with 10mgkg(-1) eucalyptol. Nontoxic eucalyptol enhanced podocyte expression of nephrin, podocin, FAT-1, CD2AP, and -actinin-4 diminished by glucose. Oral administration of eucalyptol augmented the induction of the slit diaphragm proteins, -actinin-4, and integrin 1 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 expression downregulated 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. ConclusionEucalyptol may be a potent agent antagonizing diabetes-associated malformation of interpodocyte slit junction and podocyte actin cytoskeleton.
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