論文 - 詳細
| RRC ID | 82624 |
|---|---|
| 著者 | Zhang X, Li J, Qin JJ, Cheng WL, Zhu X, Gong FH, She Z, Huang Z, Xia H, Li H. |
| タイトル | Oncostatin M receptor β deficiency attenuates atherogenesis by inhibiting JAK2/STAT3 signaling in macrophages. |
| ジャーナル | 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. |
| 巻・号 | 58(5) |
| ページ | 895-906 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02711 |