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Kidney Blood Press Res:SHMT1在磷酸盐诱导的血管平滑肌细胞钙化中的作用

2018-11-04 MedSci MedSci原创

高磷血症至少部分地通过诱导血管平滑肌细胞(VSMC)的骨- /软骨形成转分化来促进内侧血管钙化。调节该过程的复杂信号传导通路仍未完全了解。本研究调查细胞溶质丝氨酸羟甲基转移酶1(SHMT1)在磷酸盐诱导的血管钙化中的作用。 通过在原代人主动脉平滑肌细胞(HAoSMC)中沉默然后在没有磷酸盐或抗氧化剂的情况下进行治疗来抑制SHMT1的内源性表达。 结果,在HAoSMCs中,SHMT1 m

高磷血症至少部分地通过诱导血管平滑肌细胞(VSMC)的骨- /软骨形成转分化来促进内侧血管钙化。调节该过程的复杂信号传导通路仍未完全了解。本研究调查细胞溶质丝氨酸羟甲基转移酶1(SHMT1)在磷酸盐诱导的血管钙化中的作用。

通过在原代人主动脉平滑肌细胞(HAoSMC)中沉默然后在没有磷酸盐或抗氧化剂的情况下进行治疗来抑制SHMT1的内源性表达。

结果,在HAoSMCs中,SHMT1 mRNA表达被磷酸盐上调。单独SHMT1的沉默足以诱导HAoSMC的骨-/软骨形成转分化,如通过增加的组织非特异性碱性磷酸酶(ALPL)活性和成骨标志物MSX2,CBFA1和ALPL mRNA表达所示。此外,与阴性对照siRNA转染的HAoSMCs相比,SHMT1沉默的HAoSMCs中磷酸盐诱导的ALPL mRNA表达和活性以及钙化增强。SHMT1的沉默降低了总抗氧化能力,并上调了HASMCs中NADH/NADPH氧化酶系统组分NOX4和CYBA mRNA的表达,并且与基质金属蛋白酶MMP2的mRNA表达增加以及BAX/BCL2比率相平行。更重要的是,用抗氧化剂TEMPOL或TIRON进行的额外治疗减弱了SHMT1沉默的HAoSMCs中增加的成骨标志物mRNA表达。

SHMT1的沉默通过诱导细胞氧化应激至少部分地促进VSMCs中的骨-/软骨形成信号传导。因此它加重了磷酸盐诱导的VSMCs钙化。本发现支持SHMT1在高磷血症如慢性肾病的血管钙化中的调节作用。

原始出处:

Boehme B, Schelski N, et al., Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate-Induced Vascular Smooth Muscle Cell Calcification. Kidney Blood Press Res. 2018;43(4):1212-1221. doi: 10.1159/000492248. Epub 2018 Aug 2.

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1981293, encodeId=7d09198129391, content=<a href='/topic/show?id=c20f488e7cd' target=_blank style='color:#2F92EE;'>#平滑肌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48877, encryptionId=c20f488e7cd, topicName=平滑肌细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Mon Dec 03 14:20:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028558, encodeId=ee50202855896, content=<a href='/topic/show?id=35da896260d' target=_blank style='color:#2F92EE;'>#血管平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=129, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89626, encryptionId=35da896260d, topicName=血管平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=236b481, createdName=anan, createdTime=Sat Mar 09 09:20:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1691710, encodeId=b6c51691e1053, content=<a href='/topic/show?id=8ed9488e37e' target=_blank style='color:#2F92EE;'>#平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48873, encryptionId=8ed9488e37e, topicName=平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a5d29283334, createdName=shijzhiewnjhch, createdTime=Sat Jun 08 16:20:00 CST 2019, time=2019-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459923, encodeId=62ca1459923cf, content=<a href='/topic/show?id=e50ce3859fe' target=_blank style='color:#2F92EE;'>#磷酸盐#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73859, encryptionId=e50ce3859fe, topicName=磷酸盐)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d8ea6208793, createdName=chenshujs, createdTime=Tue Nov 06 12:20:00 CST 2018, time=2018-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603126, encodeId=f1431603126c4, content=<a href='/topic/show?id=81b91049067' target=_blank style='color:#2F92EE;'>#kidney#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10490, encryptionId=81b91049067, topicName=kidney)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c36e18990621, createdName=gwc389, createdTime=Tue Nov 06 12:20:00 CST 2018, time=2018-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604537, encodeId=d5c9160453edc, content=<a href='/topic/show?id=d6928962ec2' target=_blank style='color:#2F92EE;'>#血管平滑肌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89627, encryptionId=d6928962ec2, topicName=血管平滑肌细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=329e19217698, createdName=xiay994459, createdTime=Tue Nov 06 12:20:00 CST 2018, time=2018-11-06, status=1, ipAttribution=)]
    2018-11-06 gwc389
  6. [GetPortalCommentsPageByObjectIdResponse(id=1981293, encodeId=7d09198129391, content=<a href='/topic/show?id=c20f488e7cd' target=_blank style='color:#2F92EE;'>#平滑肌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48877, encryptionId=c20f488e7cd, topicName=平滑肌细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Mon Dec 03 14:20:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028558, encodeId=ee50202855896, content=<a href='/topic/show?id=35da896260d' target=_blank style='color:#2F92EE;'>#血管平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=129, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89626, encryptionId=35da896260d, topicName=血管平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=236b481, createdName=anan, createdTime=Sat Mar 09 09:20:00 CST 2019, time=2019-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1691710, encodeId=b6c51691e1053, content=<a href='/topic/show?id=8ed9488e37e' target=_blank style='color:#2F92EE;'>#平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48873, encryptionId=8ed9488e37e, topicName=平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a5d29283334, createdName=shijzhiewnjhch, createdTime=Sat Jun 08 16:20:00 CST 2019, time=2019-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459923, encodeId=62ca1459923cf, content=<a href='/topic/show?id=e50ce3859fe' target=_blank style='color:#2F92EE;'>#磷酸盐#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73859, encryptionId=e50ce3859fe, topicName=磷酸盐)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d8ea6208793, createdName=chenshujs, createdTime=Tue Nov 06 12:20:00 CST 2018, time=2018-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1603126, encodeId=f1431603126c4, content=<a href='/topic/show?id=81b91049067' target=_blank style='color:#2F92EE;'>#kidney#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10490, encryptionId=81b91049067, topicName=kidney)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c36e18990621, createdName=gwc389, createdTime=Tue Nov 06 12:20:00 CST 2018, time=2018-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604537, encodeId=d5c9160453edc, content=<a href='/topic/show?id=d6928962ec2' target=_blank style='color:#2F92EE;'>#血管平滑肌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89627, encryptionId=d6928962ec2, topicName=血管平滑肌细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=329e19217698, createdName=xiay994459, createdTime=Tue Nov 06 12:20:00 CST 2018, time=2018-11-06, status=1, ipAttribution=)]
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