RRC ID |
78829
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Author |
Chang JW, Liu SC, Lin YY, He XY, Wu YS, Su CM, Tsai CH, Chen HT, Fong YC, Hu SL, Huang CC, Tang CH.
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Title |
Nesfatin-1 Stimulates CCL2-dependent Monocyte Migration And M1 Macrophage Polarization: Implications For Rheumatoid Arthritis Therapy.
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Journal |
Int J Biol Sci
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Abstract |
Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to inflammatory events in various diseases, although its role in RA pathology is uncertain. Analysis of the Gene Expression Omnibus GSE55235 dataset revealed high levels of expression of the adipokine nesfatin-1 in human RA synovial tissue. Similarly, our human synovial tissue samples exhibited increasing levels of nesfatin-1 expression and Ccl2 mRNA expression. Nesfatin-1-induced stimulation of CCL2 expression and monocyte migration involved the MEK/ERK, p38, and NF-κB signaling pathways. Notably, nesfatin-1-induced increases in CCL2 expression favored M1 macrophage polarization, which increased the expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Finally, nesfatin-1 shRNA ameliorated the severity of inflammatory disease and reduced levels of M1 macrophage expression in CIA mice. Our studies confirm that nesfatin-1 appears to be worth targeting in RA treatment.
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Volume |
19(1)
|
Pages |
281-293
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Published |
2023-1-1
|
DOI |
10.7150/ijbs.77987
|
PII |
ijbsv19p0281
|
PMID |
36594093
|
PMC |
PMC9760434
|
MeSH |
Adipokines / metabolism
Animals
Arthritis, Rheumatoid* / genetics
Arthritis, Rheumatoid* / metabolism
Chemokine CCL2 / metabolism
Cytokines / metabolism
Humans
Macrophages / metabolism
Mice
Monocytes* / metabolism
|
Resource |
Human and Animal Cells |
MH7A(RCB1512) |