Circulation: SOX9是缺血性心肌纤维化的关键调节因子

2017-07-20 Yara MedSci原创

tomo-seq基于精确的局部表达情况,可用于鉴定涉及心脏重塑特定方面的新基因和关键转录因子。使用tomo-seq,研究人员能够揭示SOX9作为心脏纤维化的关键调节因子的未知功能,而且,SOX9可以作为心脏纤维化的潜在治疗靶点。

心脏缺血性损伤会引起病理性的心脏重塑反应,这可能会导致心力衰竭。关于心脏重构的不同方面的分子信号通路机制都将有助于发现新的治疗靶点。

尽管关于病变组织的基因组转录分析已经大大提高了我们对于驱动心脏病理变化的调节网络的理解,但是这种方法的弊端是信号来源于病变组织匀浆。最近,研究人员使用tomo-seq方法获得了从梗塞区域到远端的高空间分辨率的全基因组基因表达图谱,从而可以鉴定新的心脏重塑的调节因子,后续并使用缺血性心脏病患者的心脏组织样本对以上发现进行了验证。

跟踪梗死心脏的高空间分辨率的转录差异后,研究人员发现一些表达谱一样的基因簇。这种空间分布模式表明参与心脏重塑特定方面的基因具有独立的表达变化,如:纤维化,心肌细胞肥大和钙处理(Col1a2,Nppa和Serca2)。随后的关联分析还鉴定了一些在梗塞组织里表达谱相似的转录调控因子。这些已知的标记基因和表达共调节的基因具有很强的相关性,而且这种相关性可以在病人来源的缺血性心脏组织样品中得到证实。在随后的分析中,研究人员发现S0X9作为大部分纤维化相关基因的常见转录调节因子在缺血性损伤条件下会被激活。谱系追踪实验表明大多数COL1阳性成纤维细胞来自于表达SOX9的细胞群体,并且体内的Sox缺失抑制了缺血性损伤后的心脏纤维化反应。而且,在缺血性心脏病患者中也可以确认SOX9和COL1之间是共定位的。

tomo-seq基于精确的局部表达情况,可用于鉴定涉及心脏重塑特定方面的新基因和关键转录因子。使用tomo-seq,研究人员能够揭示SOX9作为心脏纤维化的关键调节因子的未知功能,而且,SOX9可以作为心脏纤维化的潜在治疗靶点。

原文出处
Grégory P. A. Lacraz, et al. Tomo-seq Identifies SOX9 as a Key Regulator of Cardiac Fibrosis During Ischemic Injury. Circulation, July 19, 2017.

本文系梅斯医学(MedSci)原创编译整理,转载需授权!

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1892906, encodeId=bec318929063e, content=<a href='/topic/show?id=c738e93521f' target=_blank style='color:#2F92EE;'>#缺血性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79352, encryptionId=c738e93521f, topicName=缺血性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Thu Nov 16 10:42:00 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2078014, encodeId=722120e801411, content=<a href='/topic/show?id=8a8580960a5' target=_blank style='color:#2F92EE;'>#肌纤维#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80960, encryptionId=8a8580960a5, topicName=肌纤维)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea6321, createdName=okhuali, createdTime=Mon Aug 21 16:42:00 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969254, encodeId=d63c196925463, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Dec 02 23:42:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224332, encodeId=0c7f224332d3, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Thu Jul 20 17:28:02 CST 2017, time=2017-07-20, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1892906, encodeId=bec318929063e, content=<a href='/topic/show?id=c738e93521f' target=_blank style='color:#2F92EE;'>#缺血性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79352, encryptionId=c738e93521f, topicName=缺血性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Thu Nov 16 10:42:00 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2078014, encodeId=722120e801411, content=<a href='/topic/show?id=8a8580960a5' target=_blank style='color:#2F92EE;'>#肌纤维#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80960, encryptionId=8a8580960a5, topicName=肌纤维)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea6321, createdName=okhuali, createdTime=Mon Aug 21 16:42:00 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969254, encodeId=d63c196925463, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Dec 02 23:42:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224332, encodeId=0c7f224332d3, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Thu Jul 20 17:28:02 CST 2017, time=2017-07-20, status=1, ipAttribution=)]
    2017-08-21 okhuali
  3. [GetPortalCommentsPageByObjectIdResponse(id=1892906, encodeId=bec318929063e, content=<a href='/topic/show?id=c738e93521f' target=_blank style='color:#2F92EE;'>#缺血性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79352, encryptionId=c738e93521f, topicName=缺血性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Thu Nov 16 10:42:00 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2078014, encodeId=722120e801411, content=<a href='/topic/show?id=8a8580960a5' target=_blank style='color:#2F92EE;'>#肌纤维#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80960, encryptionId=8a8580960a5, topicName=肌纤维)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea6321, createdName=okhuali, createdTime=Mon Aug 21 16:42:00 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969254, encodeId=d63c196925463, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Dec 02 23:42:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224332, encodeId=0c7f224332d3, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Thu Jul 20 17:28:02 CST 2017, time=2017-07-20, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1892906, encodeId=bec318929063e, content=<a href='/topic/show?id=c738e93521f' target=_blank style='color:#2F92EE;'>#缺血性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79352, encryptionId=c738e93521f, topicName=缺血性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Thu Nov 16 10:42:00 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2078014, encodeId=722120e801411, content=<a href='/topic/show?id=8a8580960a5' target=_blank style='color:#2F92EE;'>#肌纤维#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80960, encryptionId=8a8580960a5, topicName=肌纤维)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea6321, createdName=okhuali, createdTime=Mon Aug 21 16:42:00 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969254, encodeId=d63c196925463, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sat Dec 02 23:42:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224332, encodeId=0c7f224332d3, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Thu Jul 20 17:28:02 CST 2017, time=2017-07-20, status=1, ipAttribution=)]
    2017-07-20 三生有幸9135

    学习一下谢谢分享

    0

相关资讯

心肌纤维化是肥厚型心肌病的一种早期表现

心肌纤维化是肥厚型心肌病的一种早期表现 Myocardial Fibrosis as an Early Manifestation of Hypertrophic CardiomyopathyN Engl J Med 2010;363:552-63. August 5, 2010   Carolyn Y. Ho等 美国马萨诸塞州波士顿市布里格姆和妇女医院心血管科等   背景 心肌纤维化

JCMM:miRNA-24调节心肌梗死后心肌纤维化

心肌梗死(MI)后心肌纤维化已被确定为是心脏衰竭发展的关键因素。虽然参与心脏各种病理生理过程中失调的miRNA众所周知,但miRNA在调节心肌梗死后纤维化中的作用尚不清楚。 早期研究观察到纤维化和心肌肥厚的miR-24表达之间的关系,近日,研究人员在J Cell Mol Med杂志上发表研究评估miR-24是如何调节心肌梗死后纤维化的。使用qRT-PCR发现microRNA-24在心肌梗死的心脏

Diabetes Care:1型糖尿病患者心血管危险因素与心肌纤维化、早期心功能不全的关系

研究人员调查了在1型糖尿病患者中,心血管风险因素和早期心脏功能障碍的心肌纤维化之间的关联。该研究纳入了年龄13-39岁,没有已知心血管疾病史(CVD)(n=1,441例)的1型糖尿病参与者,这些患者被招募到糖尿病控制和并发症试验(1983-1993年)中,随后参与了糖尿病干预和并发的流行病学研究(1994年至今)。714名参与者接受了延迟钆增强心脏磁共振(CMR)成像(2007-2009),以评估

Am J Cardiol:hs-cTnT联合BNP可用于心肌纤维化检测

  日本一项研究表明,在肥厚型心肌病患者中,高敏心脏肌钙蛋白T(hs-cTnT)和脑利钠肽(BNP)联合可用于检测心肌纤维化。论文于6月10日在线发表于《美国心脏病学杂志》(Am J Cardiol)。   此项研究共纳入53例肥厚型心肌病患者,其中23例患者伴有延迟钆增强。评估血清肌红蛋白、心肌肌球蛋白轻链I、hs-cTnT、肌酸激酶MB同工酶水平和血浆BNP水平与延迟钆增

PNAS:sEH抑制剂能阻断心肌纤维化

心脏病发作后的组织损伤往往会最终导致心力衰竭,而加州大学Davis分校(UC Davis)的一项新研究,通过抑制一个促炎症的酶阻断了上述组织损伤,此外研究人员还确定了其中的分子机制。文章发表在美国国家科学院院刊PNAS杂志上。 可溶性环氧化物水解酶sEH,是组织修复相关免疫应答中的关键成员,不过在心脏病发作后,这种酶往往会产生事与愿违的影响。Chiamvimonvat解释道,sEH使促炎症的脂类

Eur Heart J:解开“僵硬心”之谜:一种新基因突变导致的心肌病

日前,国际著名心血管杂志《欧洲心脏杂志》(European heart journal)在线刊发了以中南大学湘雅二医院心血管内科彭道泉教授为通讯作者、于碧莲主治医生为第一作者的病例文章。 该文章介绍的病例是一名25岁年轻女性,因为气促浮肿进行性加重2年多,心脏B超显示其心脏极度"僵硬",曾辗转省内多家医院未能确诊。在对患者进行详细的病情评估并行心内膜活检,排除了常见的浸润性心肌病后,大胆