Mesencephalic Astrocyte-Derived Neurotrophic Factor Is Involved in Inflammation by Negatively Regulating the NF-κB Pathway

被引：125

作者：

Chen, Lijian ^{[1
,2
,3
,4
]}

Feng, Lijie ^{[2
,3
]}

Wang, Xia ^{[2
,3
]}

Du, Jian ^{[2
,3
]}

Chen, Ying ^{[3
]}

Yang, Wen ^{[1
,3
]}

Zhou, Chengyue ^{[2
,3
]}

Cheng, Li ^{[2
,3
]}

Shen, Yujun ^{[2
,3
]}

Fang, Shengyun ^{[2
,3
,5
]}

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

Shen, Yuxian ^{[2
,3
]}

机构：

[1] Anhui Med Univ, Sch Pharm, Hefei 230032, Anhui, Peoples R China

[2] Anhui Med Univ, Sch Basic Med Sci, Hefei 230032, Anhui, Peoples R China

[3] Anhui Med Univ, Inst Biopharmaceut, Hefei 230032, Anhui, Peoples R China

[4] Anhui Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Hefei 230022, Anhui, Peoples R China

[5] Univ Maryland, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

中国国家自然科学基金;

关键词：

ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ER STRESS; INDUCED APOPTOSIS; NITRIC-OXIDE; ACTIVATION; BINDING; INDUCTION; CELLS; KU80;

D O I：

10.1038/srep08133

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Inflammation can cause endoplasmic reticulum (ER) stress and therefore activates the unfolded protein response (UPR). ER stress and the consequent UPR have the potential to activate NF-kappa B. However, the factors mediating the crosstalk between ER stress and the NF-kappa B pathway remain unclear. Here, we determined that ER stress inducible protein Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) was up-regulated in autoimmune diseases and inflammatory disease models. Inflammation caused MANF to relocalize to the nuclei. MANF interacted with the DNA binding domain of p65 through its C-terminal SAP-like domain in the nuclei under the condition of inflammation or ER stress. MANF consequently inhibited p65-mediated transcriptional activation by interfering with the binding of p65 to its target genes promoters. Consistently, MANF suppressed the expressions of NF-kappa B-dependent target genes and the proliferation of inflammatory synoviocytes. These findings suggest that MANF may be a negative regulator of inflammation and mediate the crosstalk between the NF-kappa B pathway and ER stress.

引用

页数：13

共 42 条

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