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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

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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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    2018-12-03 仁心济世

    #平滑肌细胞#

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    2019-03-09 anan

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    2019-06-08 shijzhiewnjhch

    #平滑肌#

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    2018-11-06 chenshujs

    #磷酸盐#

    0

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    2018-11-06 gwc389

    #kidney#

    0

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    2018-11-06 xiay994459

    #血管平滑肌细胞#

    0