| RRC ID |
82624
|
| Author |
Zhang X, Li J, Qin JJ, Cheng WL, Zhu X, Gong FH, She Z, Huang Z, Xia H, Li H.
|
| Title |
Oncostatin M receptor β deficiency attenuates atherogenesis by inhibiting JAK2/STAT3 signaling in macrophages.
|
| Journal |
J Lipid Res
|
| Abstract |
Oncostatin M (OSM) is a secreted cytokine mainly involved in chronic inflammatory and cardiovascular diseases through binding to OSM receptor β (OSMR-β). Recent studies demonstrated that the presence of OSM contributed to the destabilization of atherosclerotic plaque. To investigate whether OSMR-β deficiency affects atherosclerosis, male OSMR-β-/-ApoE-/- mice were generated and utilized. Here we observed that OSMR-β expression was remarkably upregulated in both human and mouse atherosclerotic lesions, which were mainly located in macrophages. We found that OSMR-β deficiency significantly ameliorated atherosclerotic burden in aorta and aortic root relative to ApoE-deficient littermates and enhanced the stability of atherosclerotic plaques by increasing collagen and smooth muscle cell content, while decreasing macrophage infiltration and lipid accumulation. Moreover, bone marrow transplantation of OSMR-β-/- hematopoietic cells to atherosclerosis-prone mice displayed a consistent phenotype. Additionally, we observed a relatively reduced level of JAK2 and signal transducer and activator of transcription (STAT)3 in vivo and under Ox-LDL stimulation in vitro. Our findings suggest that OSMR-β deficiency in macrophages improved high-fat diet-induced atherogenesis and plaque vulnerability. Mech-anistically, the protective effect of OSMR-β deficiency on atherosclerosis may be partially attributed to the inhibition of the JAK2/STAT3 activation in macrophages, whereas OSM stimulation can activate the signaling pathway.
|
| Volume |
58(5)
|
| Pages |
895-906
|
| Published |
2017-5-1
|
| DOI |
10.1194/jlr.M074112
|
| PII |
S0022-2275(20)33825-6
|
| PMID |
28258089
|
| PMC |
PMC5408608
|
| MeSH |
Animals
Atherosclerosis / genetics
Atherosclerosis / metabolism*
Atherosclerosis / pathology*
Gene Expression Regulation
Gene Knockout Techniques
Humans
Janus Kinase 2 / metabolism*
Macrophages / pathology*
Male
Mice
Mice, Inbred C57BL
Necrosis / metabolism
Oncostatin M Receptor beta Subunit / deficiency*
Oncostatin M Receptor beta Subunit / genetics
Oncostatin M Receptor beta Subunit / metabolism
Plaque, Atherosclerotic / metabolism
Plaque, Atherosclerotic / pathology
STAT3 Transcription Factor / metabolism*
Signal Transduction*
|
| IF |
4.483
|
| Resource |
| Mice |
RBRC02711 |
