skip to main content

SciTech ConnectSciTech Connect

Title: Spliced XBP1 promotes macrophage survival and autophagy by interacting with Beclin-1

Macrophage autophagy plays an important role in the development of atherosclerosis, but the precise mechanism mediating this process is unclear. The potential role of the X-box binding protein 1 (XBP1), a crucial transduction factor that is involved in endoplasmic reticulum stress and the unfolded protein response, in bone marrow-derived macrophage autophagy is unknown. This study mainly explores the roles of XBP1 mRNA splicing in bone marrow-derived macrophage autophagy. The present study shows that the transient overexpression of spliced XBP1 via adenovirus-mediated gene transfer induces autophagy and promotes proliferation in bone marrow-derived macrophages via the down-regulation of Beclin-1, but that the sustained overexpression of spliced XBP1 leads to apoptosis. When XBP1 is down-regulated in bone marrow-derived macrophages using siRNA, rapamycin-induced autophagosome formation is ablated. Furthermore, we have detected the overexpression of XBP1 in areas of atherosclerotic plaques in the arteries of ApoE−/− mice. These results demonstrate that XBP1 mRNA splicing plays an important role in maintaining the function of bone marrow-derived macrophages and provide new insight into the study and treatment of atherosclerosis. - Highlights: • XBP1 was up-regulated in atherosclerotic plaques of ApoE−/− mice. • Transient spliced XBP1 overexpression induced macrophages autophagy via Beclin-1. • Sustained spliced XBP1 overexpression triggeredmore » macrophages apoptosis. • Spliced XBP1 plays a key role in maintaining the macrophages survival.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5]
  1. Southern Medical University, Guangzhou, Guangdong 510515 (China)
  2. Centre Laboratory, The 305th Hospital of the People's Liberation Army, Beijing 100017 (China)
  3. Department of Geriatric Cardiology, Chinese PLA General Hosptial, Beijing 100853 (China)
  4. Laboratory of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)
  5. Department of Cardiology, The 305th Hospital of the People's Liberation Army, Beijing 100017 (China)
Publication Date:
OSTI Identifier:
22462132
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 463; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOVIRUS; APOPTOSIS; ARTERIES; ARTERIOSCLEROSIS; BONE MARROW; ENDOPLASMIC RETICULUM; GENES; MACROPHAGES; MESSENGER-RNA; MICE; PROTEINS; SPLICING; STRESSES