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PTPN2 negatively regulates macrophage inflammation in atherosclerosis
- Source :
- Aging (Albany NY)
- Publication Year :
- 2020
- Publisher :
- Impact Journals, LLC, 2020.
-
Abstract
- Atherosclerosis is the main cause of cardiovascular disease. Systemic inflammation is one important characteristic in atherosclerosis. Pro-inflammatory macrophages can secrete inflammatory factors and promote the inflammation of atherosclerosis. It has a great value for the treatment of atherosclerosis by inhibiting the release of inflammatory factors in macrophages. However, the detailed mechanism of this process is still unclear. In this study, we constructed an APOE-/- mice model of atherosclerosis to research the molecular mechanism of atherosclerosis. Protein tyrosine phosphatase non-receptor type 2 (PTPN2), an anti-inflammatory gene, was dramatically decreased in inflammatory mice. Deletion of PTPN2 could significantly induce monocytes toward M1 phenotype of macrophages, enhance the secretion of IL-12 and IL-1, and promote cell proliferation, invasion and metastasis. Mechanism research showed that PTPN2-mediated p65/p38/STAT3 de-phosphorylation could block the process of macrophage inflammation. In vivo experiments showed that PTPN2 may effectively inhibit the inflammatory response during atherosclerosis. In conclusion, we uncovered the negative role of PTPN2 in the occurrence of atherosclerosis, and this study provides a new potential target for atherosclerosis treatment.
- Subjects :
- STAT3 Transcription Factor
Aging
Mice, Knockout, ApoE
THP-1 Cells
p38 mitogen-activated protein kinases
Interleukin-1beta
Inflammation
macrophage
Protein tyrosine phosphatase
Systemic inflammation
p38 Mitogen-Activated Protein Kinases
Mice
Cell Movement
medicine
Animals
Humans
Macrophage
Secretion
RNA, Messenger
STAT3
Cell Proliferation
Protein Tyrosine Phosphatase, Non-Receptor Type 2
biology
Interleukin-6
Cell growth
business.industry
Macrophages
Transcription Factor RelA
U937 Cells
Cell Biology
Atherosclerosis
Interleukin-12
Cancer research
biology.protein
PTPN2
medicine.symptom
business
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....ad8c723481e1e5d32fba8b4276098672