脂质过氧化
氧化应激
化学
TBARS公司
内分泌学
下调和上调
内科学
生物化学
生物
医学
基因
作者
Xiaoe Fan,Manhong Xu,Qianfeng Ren,Yan Fan,Boshi Liu,Jiaqi Chen,Zhengmin Wang,Xiaoyan Sun
出处
期刊:Bioengineered
[Informa]
日期:2022-04-01
卷期号:13 (4): 10540-10551
被引量:34
标识
DOI:10.1080/21655979.2022.2062533
摘要
This study aims to explore the role of fatty acid binding protein 4 (FABP4) in diabetic retinopathy (DR), and to elucidate the potential regulatory mechanism. We firstly developed a mouse model of DR by injection with streptozocin (STZ) into C57BL/6 male mice and a cell model of DR by induction of high glucose (HG) to ARPE-19 cells. BMS309403, an inhibitor of FABP4, was employed for treatment. The blood glucose in vivo was monitored and the histological changes of retinal tissues were observed by hematoxylin and eosin staining and Evans blue assay. The expression level of FABP4 was detected by western blot and Immunohistochemical staining. The critical factors related to lipid peroxidation and oxidative stress were detected using their commercial kits, respectively. Prussian blue staining, iron content assay and thiobarbituric acid-reactive substances (TBARS) assay were conducted to evaluate ferroptosis. As a result, FABP4 was elevated in retina and serum of STZ-induced mice and in HG-induced ARPE-19 cells. BMS309403 treatment notably alleviated reduced blood glucose, reduced histological damage, and vascular permeability. In addition, BMS309403 treatment inhibited lipid peroxidation, oxidative stress, and ferroptosis both in vivo and in vitro. Furthermore, BMS309403 promoted the activation of peroxisome proliferator-activated receptor γ (PPARγ). GW9662 (an inhibitor of PPARγ) or Erastin (an inducer of ferroptosis) partially weakened the suppressive effects of BMS309403 on HG-induced lipid peroxidation, oxidative stress and ferroptosis. Taken together, FABP4 inhibition alleviates lipid peroxidation and oxidative stress in DR by regulating PPARγ-mediated ferroptosis.
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