期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1833, 期 12, 页码 3386-3395出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2013.10.011
关键词
Advanced glycation end-products; Lipocalin-2; Human aortic smooth muscle cells; Migration; Invasion
资金
- Research Fund Program of the Research Institute for Basic Sciences, Pusan National University, Korea [RIBS-PNU-2012-112]
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2012R1A1A1005392]
- National Research Foundation of Korea [2012R1A1A1005392] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Advanced glycation end-products (AGEs) play key roles in the development of diabetic vascular complications by activating the proliferation and migration of vascular smooth muscle cells. Here, we identified an increase of the migratory properties of human aortic smooth muscle cells (HASMC) through AGE-induced expression of lipocalin-2 (LCN2). Because the AGE-elicited expression of LCN2 was diminished by an antibody against the AGE receptor (RAGE), diphenylene iodonium (DPI), N-acetyl cysteine, LY294002, and SP600125, we suggest that AGEs enhance the expression of LCN2 via a RAGE-NADPH oxidase-reactive oxygen species pathway, leading to the phosphorylation of PI3K-Akt and JNK in HASMCs. In addition, a chromatin immunoprecipitation assay and promoter assay revealed that CCAAT/enhancer binding protein 13 is crucial for AGE-induced expression of LCN2. However, any other AGE-related signaling pathway, including ERK1/2, p38, NP-kappa B, and AP-1, did not affect the AGE- induced expression of LCN2. Knockdown of LCN2 expression by shRNA showed that AGE-elicited LCN2 expression enhanced the invasive and migratory properties of HASMCs, but showed no effect on cell proliferation. Considering the importance of HASMC migration in the development of atherosclerosis, our study provides a novel insight into diabetic vascular complications. (C) 2013 Elsevier B.V. All rights reserved.
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