title: Spliced XBP1 promotes macrophage survival and autophagy by interacting with Beclin-1.
abstract: 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.
authors.affiliation: Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Ping-Ge
authors.initials: PG
authors.lastname: Tian
authors.affiliation: Centre Laboratory, The 305th Hospital of the People's Liberation Army, Beijing 100017, China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Jiang
authors.affiliation: Department of Geriatric Cardiology, Chinese PLA General Hosptial, Beijing 100853, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Li
authors.affiliation: Laboratory of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: zhouzhe76@126.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The 305th Hospital of the People's Liberation Army, Beijing 100017, China. Electronic address: 1056055170@qq.com.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D001343:Autophagy / Q000235:genetics*; D001483:Base Sequence; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000071717:X-Box Binding Protein 1
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse
keywords: Autophagy; Macrophage; Proliferation; X-box binding protein 1