Chrysin ameliorates podocyte injury and slit diaphragm protein loss via inhibition of the PERK-elF2α-ATF-CHOP pathway in diabetic mice

Iomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular Itration barrier via their foot processes. Chrysin （5,7-dihydroxyflavone） is a natural flavonoid found in propolis and mushrooms that has nti-inflammatory, antioxidan...

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Published in:中国药理学报：英文版 2017, Vol.38 (8), p.1129-1140
Main Author: Min-Kyung KANG Sin-Hye PARK Yun-Ho KIM Eun-Jung LEE Lucia Dwi ANTIKA DongYeon KIM Yean-Jung CHOi Young-Hee KANG
Format: Article
Language:English
Subjects:
f2α
内质网应激
小鼠
损失
白杨素
糖尿病大鼠
细胞损伤
膜蛋白
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Summary:Iomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular Itration barrier via their foot processes. Chrysin （5,7-dihydroxyflavone） is a natural flavonoid found in propolis and mushrooms that has nti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte poptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys. Exposure to igh glucose （33 mmol/L） caused glomerular podocyte apoptosis in vitro, which was dose-dependently attenuated by nontoxic chrysin 1-20 pmol/L） through reduction of DNA fragmentation. Chrysin treatment dose-dependently restored the increased Bax/Bcl-2 ratio, and suppressed Apaf-1 induction and the elevated cytochrome c release in high glucose-exposed renal podocytes. In diabetic db/db nice, oral administration of chrysin （10 mg·kg^-1·d^-1, for 10 weeks） significantly attenuated proteinuria, and alleviated the abnormal ilterations in glomerular ultrastructure, characterized by apoptotic podocytes and foot process effacement. In addition, this compound reproved the induction of slit diaphragm proteins podocin/nephrin in the diabetic glomeruli. Exposure to high glucose elevated the infolded protein response （UPR） to ER stress in renal podocytes, evidenced by up-regulation of PERK-elF2α-ATF4-CHOR Chrysin ：reatment blocked such ER stress responses pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins in vitro and in vivo. These observations demonstrate that targeting ER stress is an underlying mechanism of chrysin-mediated amelioration of diabetes-associated podocyte injury and dysfunction.
ISSN:1671-4083
1745-7254