Unknown

Dataset Information

0

Intracellular XBP1-IL-24 axis dismantles cytotoxic unfolded protein response in the liver.


ABSTRACT: Endoplasmic reticulum (ER) stress-associated cell death is prevalent in various liver diseases. However, the determinant mechanism how hepatocytes survive unresolved stress was still unclear. Interleukin-24 (IL-24) was previously found to promote ER stress-mediated cell death, and yet its expression and function in the liver remained elusive. Here we identified an antiapoptotic role of IL-24, which transiently accumulated within ER-stressed hepatocytes in a X-box binding protein 1 (XBP1)-dependent manner. Disruption of IL-24 increased cell death in the CCL4- or APAP-challenged mouse liver or Tm-treated hepatocytes. In contrast, pharmaceutical blockade of eukaryotic initiation factor 2? (eIF2?) or genetical ablation of C/EBP homologous protein (CHOP) restored hepatocyte function in the absence of IL-24. In a clinical setting, patients with acute liver failure manifested a profound decrease of hepatic IL-24 expression, which was associated with disease progression. In conclusion, intrinsic hepatocyte IL-24 maintains ER homeostasis by restricting the eIF2?-CHOP pathway-mediated stress signal, which might be exploited as a bio-index for prognosis or therapeutic intervention in patients with liver injury.

SUBMITTER: Wang J 

PROVIDER: S-EPMC6944701 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Intracellular XBP1-IL-24 axis dismantles cytotoxic unfolded protein response in the liver.

Wang Jianye J   Hu Bian B   Zhao Zhicong Z   Zhang Haiyan H   Zhang He H   Zhao Zhenjun Z   Ma Xiong X   Shen Bin B   Sun Beicheng B   Huang Xingxu X   Hou Jiajie J   Xia Qiang Q  

Cell death & disease 20200106 1


Endoplasmic reticulum (ER) stress-associated cell death is prevalent in various liver diseases. However, the determinant mechanism how hepatocytes survive unresolved stress was still unclear. Interleukin-24 (IL-24) was previously found to promote ER stress-mediated cell death, and yet its expression and function in the liver remained elusive. Here we identified an antiapoptotic role of IL-24, which transiently accumulated within ER-stressed hepatocytes in a X-box binding protein 1 (XBP1)-depende  ...[more]

Similar Datasets

| S-EPMC6251307 | biostudies-literature
| S-EPMC5025885 | biostudies-literature
2018-12-06 | GSE119427 | GEO
| S-EPMC4563737 | biostudies-literature
| S-EPMC4020088 | biostudies-other
| S-SCDT-EMBOJ-2022-111952 | biostudies-other
| S-EPMC5645705 | biostudies-literature
2017-01-17 | GSE86048 | GEO
| S-EPMC2963107 | biostudies-literature
| S-EPMC9670206 | biostudies-literature