Hepatology：酪氨酸激酶SYK是肝纤维化的潜在治疗靶点

2018-03-18 MedSci MedSci原创

SYK通过活化HSCs促进肝纤维化，是抗肝纤维化和预防HCC发展的潜在治疗靶点。

研究背景：脾酪氨酸激酶（SYK）在免疫细胞信号通路中起着关键作用，已被报告为人类肝细胞癌（HCC）的一种新的生物标记物。本研究旨在调查SYK促进肝纤维化的机制，并评估SYK是否可作为肝纤维化的治疗靶点。

研究方法：该研究评估了SYK的细胞定位和SYK表达与正常、HBV感染、HCV感染和非酒精性脂肪肝炎(NASH)肝组织肝纤维化的(n=36、127、22和30)相关性。采用PCR方法检测SYK敲除后，肝星状细胞(HSCs)中转录因子表达的变化。在LX-2细胞、TWNT-4细胞、原代人类HSCs和3个进展性纤维化/肝硬化动物模型(包括四氯化碳小鼠模型、二乙基亚硝胺和胆管结扎大鼠模型)中，研究了SYK拮抗剂对肝纤维化的影响。

研究结果：研究发现HSCs和肝细胞中的SYK蛋白与人肝组织中的肝纤维化阶段呈正相关。HBV或HCV感染显著增加肝细胞中SYK和细胞因子的表达。增加的细胞因子进一步诱导了肝星状细胞中SYK的表达和肝纤维化相关细胞因子的转录。在HSCs中上调的SYK通过增加了与激活HSCs相关的转录因子的表达，从而促进HSC的激活。SYK拮抗剂通过抑制HSC激活，有效抑制肝纤维化，降低阻塞性黄疸，降低HCC在动物模型中的发展。

研究结论：SYK通过活化HSCs促进肝纤维化，是抗肝纤维化和预防HCC发展的潜在治疗靶点。

原始出处

Qu C， Zheng D， Li S， et al. Tyrosine Kinase SYK is a Potential Therapeutic Target for Liver Fibrosis. Hepatology， 2018， Mar 14. doi： 10.1002/hep.29881.

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2018-07-12 luckyshitiancai_42705695

#酪氨酸激酶#

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2018-05-06 jj000001

#肝纤维#

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2018-09-03 drj2003

#治疗靶点#

75 0
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2018-03-20 gwc384

#EPA#

89 0
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2018-03-20 redcrab

#激酶#

98 0
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2018-03-18 有备才能无患

脾酪氨酸激酶(SYK)在免疫细胞信号通路中起着关键作用.已被报告为人类肝细胞癌(HCC)的一种新的生物标记物.本研究旨在调查SYK促进肝纤维化的机制.并评估SYK是否可作为肝纤维化的治疗靶点.

128 0
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2018-03-18 sunfeifeiyang

阅

133 0
[GetPortalCommentsPageByObjectIdResponse(id=1740641, encodeId=11a51e40641b6, content=<a href='/topic/show?id=fd0a95511dd' target=_blank style='color:#2F92EE;'>#酪氨酸激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95511, encryptionId=fd0a95511dd, topicName=酪氨酸激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=22af34798690, createdName=luckyshitiancai_42705695, createdTime=Thu Jul 12 10:57:00 CST 2018, time=2018-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1808198, encodeId=57b11808198dc, content=<a href='/topic/show?id=f94d81342e5' target=_blank style='color:#2F92EE;'>#肝纤维#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81342, encryptionId=f94d81342e5, topicName=肝纤维)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Sun May 06 19:57:00 CST 2018, time=2018-05-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1895364, encodeId=14281895364a0, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Mon Sep 03 13:57:00 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427047, encodeId=ce88142e04788, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Tue Mar 20 12:57:00 CST 2018, time=2018-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496007, encodeId=9351149600ec1, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Tue Mar 20 12:57:00 CST 2018, time=2018-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=297516, encodeId=c3e329e5169f, content=脾酪氨酸激酶(SYK)在免疫细胞信号通路中起着关键作用.已被报告为人类肝细胞癌(HCC)的一种新的生物标记物.本研究旨在调查SYK促进肝纤维化的机制.并评估SYK是否可作为肝纤维化的治疗靶点., beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Sun Mar 18 23:19:48 CST 2018, time=2018-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=297494, encodeId=988029e494be, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=133, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Sun Mar 18 22:32:54 CST 2018, time=2018-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=297478, encodeId=710a29e47863, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, 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=Sun Mar 18 22:23:42 CST 2018, time=2018-03-18, status=1, ipAttribution=)]
2018-03-18 天地飞扬

了解一下.谢谢分享!

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Hepatology：酪氨酸激酶SYK是肝纤维化的潜在治疗靶点

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