Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 298

P08-040 - Blockade of high glucose-induced glomerular fibrosis by tangeretin through inducing autophagy

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis and tubular fibrosis, eventually causing kidney failure. Emerging body of evidence suggests that targeting the autophagic pathway to restore autophagy activity may be renoprotective.

Tangeretin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study explored the involvement of autophagy in glomerular fibrosis, and investigated effects of tangeretin on glomerular fibrosis and autophagy restoration through inhibition of PI3K/AKT/mTOR pathway.




Methods:
Human renal mesangial cells were exposed to 33 mM glucose in the absence and presence of 1-20 μM tangeretin up to 6 d. Cellular expression levels of the fibrogenic collagen-I and the autophagy-related proteins of beclin-1, LC3, P62/SQSTM1 and VPS34 were examined. In addition, PI3K, AKT and mTOR gene proteins were screened to reveal the relationship among PI3K/AKT/mTOR signaling pathway, autophagy and glomerular fibrosis.




Results:
High glucose promoted the production of collagen-1 in mesangial cells, which was dose-dependently inhibited by 1-20 μM tangeretin. Western blot data showed that high glucose elevated the expression of the autophagy marker beclin-1 and autophagosome formation protein LC3 in a temporal manner. When tangeretin was supplemented to mesangial cells exposed to high glucose, the expression of beclin-1, LC3 and P62/SQSTM1 was dampened. Also, the autophagy-specific VPS34 was down-regulated by treating tangeretin to mesangial cells stimulated by high glucose. Finally, PI3K, AKT and mTOR were activated in high glucose-exposed mesangial cells, and such activation was encumbered by tangeretin.




Conclusions:
These results demonstrated that tangeretin blunted glomerular fibrosis and restored autophagy via inhibition of PI3K/AKT/mTOR pathway. Tangeretin may be a potent renoprotective agent counteracting diabetes-associated glomerular fibrosis leading to kidney failure.




Funding Source:

This work was supported by the National Research Foundation of Korea grant funded by the Korea government (NRF-2017R1A6A3A04011473).


CoAuthors: Jung Han Yoon Park – Hallym university; Young-Hee Kang – Hallym university

Min kyung Kang

research professor
Hallym university
Chuncheon, Kangwon-do, Republic of Korea