RP5-833A20.1/miR-382-5p/NFIA–Dependent Signal Transduction Pathway Contributes to the Regulation of Cholesterol Homeostasis and Inflammatory Reaction
| Autor: | Jun-Yao Yang, Jin-Lan Huang, Shao-Guo Wu, Lei Zheng, Ya-Rong Hu, Shu-Fen Li, Zhi-Ping Chen, Xin Ma, Yan-Wei Hu, Yan-Hua Sha, Jia-Yi Zhao, Yan-Chao Wang, Yu-Rong Qiu, Ji-Juan Gao, Qian Wang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Time Factors Genetic Vectors Biology Transfection Receptor Angiotensin Type 1 Proinflammatory cytokine Apolipoproteins E Downregulation and upregulation Animals Homeostasis Humans Gene Regulatory Networks Oligonucleotide Array Sequence Analysis Inflammation Mice Knockout Regulation of gene expression Gene Expression Profiling Lentivirus Reverse cholesterol transport Gene Transfer Techniques Hep G2 Cells Atherosclerosis Long non-coding RNA Lipoproteins LDL Mice Inbred C57BL Disease Models Animal MicroRNAs NFI Transcription Factors Cholesterol Gene Expression Regulation NFIA Immunology Cancer research Cytokines RNA Long Noncoding Tumor necrosis factor alpha Caco-2 Cells Inflammation Mediators Signal transduction Cardiology and Cardiovascular Medicine Foam Cells Signal Transduction |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 35:87-101 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.114.304296 |
| Popis: | Objective— Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear. Approach and Results— Using microarray analysis, we found that long noncoding RNA RP5-833A20.1 expression was upregulated, whereas nuclear factor IA (NFIA) expression was downregulated in human acute monocytic leukemia macrophage–derived foam cells. Moreover, we showed that long noncoding RNA RP5-833A20.1 may decreases NFIA expression by inducing hsa-miR-382-5p expression in vitro. We found that the RP5-833A20.1/hsa-miR-382-5p/NFIA pathway is essential to the regulation of cholesterol homeostasis and inflammatory responses in human acute monocytic leukemia macrophages. Lentivirus-mediated NFIA overexpression increased high-density lipoprotein cholesterol circulation, reduced low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol circulation, decreased circulation of inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein, enhanced reverse cholesterol transport, and promoted regression of atherosclerosis in apolipoprotein E–deficient mice. Conclusions— Our findings indicated that the RP5-833A20.1/miR-382-5p/NFIA pathway was essential to the regulation of cholesterol homeostasis and inflammatory reactions and suggested that NFIA may represent a therapeutic target to ameliorate cardiovascular disease. |
| Databáze: | OpenAIRE |
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