Mangiferin alleviates endoplasmic reticulum stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis

被引：13

作者：

Li, Shaoxun ^{[1
,2
,3
]}

Jin, Shuanghong ^{[1
,2
,3
]}

Chen, Weilai ^{[4
]}

Yu, Jiake ^{[2
,3
,5
]}

Fang, Peipei ^{[1
,2
,5
]}

Zhou, Guangyao ^{[1
,2
]}

Li, Jie ^{[1
,2
]}

Jin, Lingxiang ^{[1
,2
]}

Chen, Yiping ^{[2
,5
]}

Chen, Ping ^{[6
,7
]}

Pan, Chenwei ^{[1
,2
,5
]}

机构：

[1] Wenzhou Med Univ, Dept Infect Dis, Affiliated Hosp 2, 109 West Coll Rd, Wenzhou 325027, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Yuying Childrens Hosp, 109 West Coll Rd, Wenzhou 325027, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Sch Med 2, Dept Infect Dis, 109 West Coll Rd, Wenzhou 325027, Zhejiang, Peoples R China

[4] Wenzhou Peoples Hosp, Dept Neurol, 57 Canghou Rd, Wenzhou 325000, Zhejiang, Peoples R China

[5] Wenzhou Med Univ, Dept Pediat Hepatitis & Liver Dis, Affiliated Hosp 2, 109 West Coll Rd, Wenzhou 325027, Zhejiang, Peoples R China

[6] Shulan Hosp, Dept Infect Dis, 848 Dongxin Rd, Hangzhou 310006, Zhejiang, Peoples R China

[7] Third Peoples Hosp Zhengzhou, Dept Infect Dis, 136 Nanshuncheng Rd, Zhengzhou 450000, Henan, Peoples R China

来源：

JOURNAL OF BIOCHEMISTRY | 2020年 / 168卷 / 04期

关键词：

acute liver injury; endoplasmic reticulum stress; mangiferin; miR-20a; miR-101a; OXIDATIVE STRESS; EPITHELIAL-CELLS; NRF2; PATHWAY; ER STRESS; PROTECTS; DAMAGE; INFLAMMATION; INVOLVEMENT; ACID;

D O I：

10.1093/jb/mvaa056

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3'-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.

引用

页码：365 / 374

页数：10

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