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.
['Tian|Ping-Ge|PG|', 'Jiang|Zhi-Xin|ZX|', 'Li|Jian-Hua|JH|', 'Zhou|Zhe|Z|', 'Zhang|Qing-Hua|QH|']
D000818:Animals D050197:Atherosclerosis D001343:Autophagy D001483:Base Sequence D049109:Cell Proliferation D002470:Cell Survival D002478:Cells, Cultured D017931:DNA Primers D004268:DNA-Binding Proteins D008264:Macrophages D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D012326:RNA Splicing D012333:RNA, Messenger D000071701:Regulatory Factor X Transcription Factors D020133:Reverse Transcriptase Polymerase Chain Reaction D014157:Transcription Factors D000071717:X-Box Binding Protein 1
Macrophage Autophagy X-box binding protein 1 Proliferation