LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells
Abstract
Objective Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently discovered novel hepatokine, leading to skeletal muscle insulin resistance by activating c-Jun N-terminal kinase (JNK). However, its role in atherosclerotic inflammatory reactions has not been examined. Therefore, we investigated the function of LECT2 on the expression of vascular adhesion molecules and inflammatory cytokines in human endothelial cells.Methods Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were treated with various doses of LECT2 and the functions and signaling pathways were analyzed through Western blot and quantitative real-time PCR (qPCR).Results The level of phosphorylated c-Jun N-terminal kinases (JNK) was significantly increased by LECT2 treatment in HUVECs and THP-1 cells, an effect that was not seen in cells treated with CD209 siRNA, a known LECT2 receptor. LECT2 treatment efficiently increased the expression of intercellular adhesion molecule-1 (ICAM-1) and pro-inflammatory cytokines tumor necrosis factor α (TNFα), monocyte chemo-attractant protein-1 (MCP-1), and interleukin-1β (IL-1β) in HUVECs and THP-1 cells. However, all these reactions were significantly reduced in response to treatment with JNK inhibitor. Furthermore, LECT2 treatment significantly exacerbated the adhesion of monocytic cells to human endothelial cells, which was also efficiently attenuated by JNK inhibitor.Conclusions LECT2 significantly induced adhesion molecules and pro-inflammatory cytokines in HUVECs via CD209-mediated JNK phosphorylation, suggesting that liver-derived novel hepatokine, LECT2, might directly mediate in the atherosclerotic inflammatory reactions in human endothelial cells.
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LECT2 alters insulin signaling through the JNK pathway in myocytes, and expression of LECT2 in liver is negatively regulated by AMPK.
“LECT2 alters insulin signaling through the JNK pathway in myocytes, and the expression of LECT2 in the liver is negatively regulated by the energy-depletion sensor AMPK [239,248,249].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [248]
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- Authors
- Hwang, H.-J., Jung, T. W., Hong, H. C., Seo, J. A., Kim, S. G., Kim, N. H., Choi, K. M., Choi, D. S., Baik, S. H., & Yoo, H. J.
- Affiliations
- Korea University (KR)
- Corresponding author
- Yoo, Hye Jin
- ORCID
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 64
- Issue
- 9
- Pages
- 1175-1182
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W1891585568
- Cited by
- 60
- References
- 27
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 5
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea University Guro Hospital (O1500061)
- National Research Foundation of Korea
- Ministry of Education, Science and Technology (2012R1A1A1005257)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- LECT2, hepatokines, atherosclerosis, endothelial inflammation, JNK phosphorylation, ICAM-1, inflammatory cytokines, TNF-α, MCP-1, IL-1β, endothelial cells, JNK inhibitor
- MeSH terms
- DC-Specific ICAM-3 Grabbing Nonintegrin, Humans, Inflammation, Phosphorylation, Receptors, Cell Surface, Cell Adhesion Molecules, Cytokines, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Lectins, C-Type, Endothelial Cells, Protein Kinase Inhibitors, JNK Mitogen-Activated Protein Kinases, Atherosclerosis, Gene Knockdown Techniques, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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