Paeonol up-regulates CKIP-1 to resist high glucose-induced fibrosis in glomerular mesangial cells
10.3969/j.issn.1001-1978.2018.05.012
- VernacularTitle:丹皮酚激活CKIP-1对高糖诱导的肾小球系膜细胞纤维化的影响
- Author:
Lei ZHANG
1
;
Ye-Zi ZOU
;
Wen-Yan GONG
;
Zhi-Quan CHEN
;
He-Qing HUANG
Author Information
1. 中山大学药学院药理与毒理学实验室
- Keywords:
paeonol;
high glucose;
CKIP-1;
Nrf2;
fi-bronectin;
glomerular mesangial cells;
renal fibrosis
- From:
Chinese Pharmacological Bulletin
2018;34(5):645-650
- CountryChina
- Language:Chinese
-
Abstract:
Aim To observe whether paeonol can in-hibit fibronectin (FN) and intercellular cell adhension molecule-1 (ICAM-1) expressions in high glucose (HG)-induced glomerular mesangial cells(GMCs) via up-regulating CKIP-1 and activating the Nrf2 signaling pathway. Methods The effects of paeonol on the ex-pressions of CKIP-1,Nrf2,FN and ICAM-1 were eval-uated in GMCs treated with HG. Small interfering RNA was used to deplete CKIP-1 protein expression, and Western bolt was used to detect the expressions of Nrf2, HO-1 and SOD1. DHE fluorescent probe tech-nique was used to determine intracellular superoxide level. Results The protein levels of CKIP-1 and Nrf2 were elevated by paeonol in HG-treated GMCs. In the meanwhile,the expressions of Nrf2 downstream antiox-idant enzymes, i.e. HO-1 and SOD1, were also up-regulated by paeonol, which was accompanied by re-ductions of superoxide and H2O2levels. Importantly, paeonol reversed the excessive accumulation of FN and ICAM-1 in HG-induced GMCs. si-CKIP-1 decreased the up-regulation of Nrf2,HO-1 and SOD1 expressions during paeonol treatment, which was accompanied by increased superoxide and H2O2levels. Furthermore, si-CKIP-1 reversed the down-regulated levels of FN and ICAM-1 induced by paeonol. Conclusion Pae-onol inhibits the expressions of FN and ICAM-1 in HG-treated GMCs possibly by up-regulating CKIP-1 and activating the Nrf2 signaling pathway.
