Circulation：IL-10-STAT3-半乳凝素-3轴对心肌梗死后产生OPN的修复性巨噬细胞极化至关重要

2018-11-03 MedSci MedSci原创

现已知骨桥蛋白（OPN）和半乳凝素-3均参与伤口愈合过程中死亡细胞的吞噬清除和修复性纤维化；CD206+巨噬细胞通过吞噬和纤维化参与心肌梗死（MI）后的组织修复。但OPN、半乳凝素-3和巨噬细胞极化在MI环境中的关系尚不明确。心肌梗死后第3天，心肌Spp1(编码OPN的基因)出现明显的激活。为明确心肌梗死后，Spp1的转录活性在哪种细胞中增强，研究人员对心肌梗死后第3天的EGFP-Spp1敲进（K

现已知骨桥蛋白（OPN）和半乳凝素-3均参与伤口愈合过程中死亡细胞的吞噬清除和修复性纤维化；CD206+巨噬细胞通过吞噬和纤维化参与心肌梗死（MI）后的组织修复。但OPN、半乳凝素-3和巨噬细胞极化在MI环境中的关系尚不明确。

心肌梗死后第3天，心肌Spp1(编码OPN的基因)出现明显的激活。为明确心肌梗死后，Spp1的转录活性在哪种细胞中增强，研究人员对心肌梗死后第3天的EGFP-Spp1敲进（KI）受体小鼠进行分析。结果显示Spp1的转录活性仅在梗死心肌内的CD206+巨噬细胞中增强，而且大部分CD206+巨噬细胞在心肌梗死后有较强的Spp1转录激活。

梗死心肌的巨噬细胞中Lgal3(编码半乳凝素-3)的时间表达谱与Spp1相似，OPN几乎完全由半乳凝素-3^[hi]CD206+巨噬细胞产生。既往报道IL-4和IL-10可促进CD206+巨噬细胞介导的心梗后的心肌修复，但本研究显示仅IL-10可刺激CD11b+Ly6G-细胞分化成产生OPN的半乳凝素-3[hi]CD206+巨噬细胞，表现出增强的吞噬能力，而IL-4无此效应。抑制STAT3酪氨酸磷酸化可抑制IL-10诱导的胞内半乳凝素-3的表达和Spp1的转录激活。敲低半乳凝素-3可抑制其分化成产生OPN的细胞，但STAT3激活不能。STAT3的酪氨酸磷酸化和半乳凝素-3^[hi]CD206+细胞在Spp1敲除小鼠的心脏CD11b+Ly6G-细胞上的出现率均与在野生型小鼠中的一致。Spp1敲除小鼠易出现心梗后左心室扩张，而且梗死心肌中TUNEL标记的阳性细胞（即凋亡细胞）也多于野生型小鼠的。

OPN几乎完全是由半乳凝素-3^[hi]CD206+巨噬细胞产生，特别是在心肌梗死后的梗死心肌中。IL-10-STAT3-半乳凝素-3轴是心肌梗死后产生OPN的修复性巨噬细胞极化的关键，这些巨噬细胞通过促进纤维化和凋亡细胞清除促进组织修复。本研究表明半乳凝素-3或可通过控制OPN水平促进梗死心肌的修复性纤维化。

原始出处：

Kohsuke Shirakawa，et al. IL (Interleukin)-10–STAT3–Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction. 24 Jul 2018. Circulation. 2018；138：2021–2035

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2019-01-03 liuxiaona

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2018-11-05 李研东

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2018-11-05 jjjiang0202

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2018-11-05 xiaoyeshuang

#IL-10#

42 0
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2018-11-05 tastas

#细胞极化#

41 0
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2018-11-03 天地飞扬

了解一下，谢谢分享！

55 0
[GetPortalCommentsPageByObjectIdResponse(id=2086573, encodeId=5a7120865e381, content=<a href='/topic/show?id=094913426c7' target=_blank style='color:#2F92EE;'>#OPN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13426, encryptionId=094913426c7, topicName=OPN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cb3a261, createdName=liuxiaona, createdTime=Thu Jan 03 16:21:00 CST 2019, time=2019-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348965, encodeId=062b13489658a, content=<a href='/topic/show?id=684f16e52c8' target=_blank style='color:#2F92EE;'>#STAT3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16752, encryptionId=684f16e52c8, topicName=STAT3)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6e7948, createdName=李研东, createdTime=Mon Nov 05 07:21:00 CST 2018, time=2018-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1508226, encodeId=d67a150822693, content=<a href='/topic/show?id=8d4596248e' target=_blank style='color:#2F92EE;'>#IL-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9624, encryptionId=8d4596248e, topicName=IL-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cf9946833, createdName=jjjiang0202, createdTime=Mon Nov 05 07:21:00 CST 2018, time=2018-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1587644, encodeId=6022158e64473, content=<a href='/topic/show?id=a6f6962576' target=_blank style='color:#2F92EE;'>#IL-10#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9625, encryptionId=a6f6962576, topicName=IL-10)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a8cd17536453, createdName=xiaoyeshuang, createdTime=Mon Nov 05 07:21:00 CST 2018, time=2018-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597878, encodeId=5ff8159e87856, content=<a href='/topic/show?id=b1e3e7926ba' target=_blank style='color:#2F92EE;'>#细胞极化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77926, encryptionId=b1e3e7926ba, topicName=细胞极化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e318558301, createdName=tastas, createdTime=Mon Nov 05 07:21:00 CST 2018, time=2018-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351410, encodeId=9370351410e6, content=了解一下，谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Sat Nov 03 20:43:16 CST 2018, time=2018-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=351389, encodeId=56ad35138959, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sat Nov 03 17:35:18 CST 2018, time=2018-11-03, status=1, ipAttribution=)]
2018-11-03 清风拂面

谢谢分享学习

39 0

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