High-mobility group box-1 promotes vascular calcification in diabetic mice via endoplasmic reticulum stress.
High-mobility group box-1 promotes vascular calcification in diabetic mice via endoplasmic reticulum stress.
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高动力组Box-1通过内质网应激促进糖尿病小鼠的血管钙化。
DOI：
10.1111/jcmm.16075
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发表时间：
2021-04
影响因子：
5.3
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Chen Z;Li R;Pei LG;Wei ZH;Xie J;Wu H;Xu B
一些研究报道了内质网应激(ERS)在血管钙化中的作用。高迁移率族蛋白-1(HMGB-1)在糖尿病及其并发症中起重要作用。然而，关于HMGB-1和钙化之间的联系的信息相对较少，潜在的机制仍然难以捉摸。因此，在本研究中，我们试图表明HMGB-1是否可以通过ERS促进糖尿病患者的血管钙化。链脲佐菌素(STZ)诱导小鼠糖尿病后，给予甘草酸(Gly)或4-苯基丁酸酯(4-PBA)治疗。逆转录-聚合酶链式反应(RT-PCR)和钙离子测定证实矿物质沉积。在细胞实验中，采用茜素红染色、碱性磷酸酶(ALP)活性和RT-PCR检测血管平滑肌细胞(VSMCs)的钙化情况。用Western blotting、免疫细胞化学(ICC)和免疫组织化学(IHC)方法检测HMGB-1在主动脉组织中的表达和定位。糖尿病小鼠表现出HMGB-1表达增加、ERS和血管钙化。然而，用甘氨酸抑制HMGB-1或用4-PBA抑制ERS可改善糖尿病小鼠血管钙化增强和ERS。体外实验表明，抑制HMGB-1可减弱晚期糖基化终末产物(AGEs)诱导的VSMC内皮细胞激活的ERS。此外，AGEs可促进VSMC中HMGB-1的转位和分泌，而4-PBA可逆转这一作用。此外，在HMGB-1和AGEs的作用下，VSMCs的矿化和成骨基因表达增加。然而，4-PBA抑制ERS可显著减轻HMGB-1诱导的VSMC钙化。因此，糖尿病通过ERS诱导HMGB-1的转位和分泌，从而导致糖尿病小鼠和AGEs处理的VSMC发生钙化。
Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High‐mobility group box‐1 (HMGB‐1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB‐1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB‐1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4‐phenylbutyrate (4‐PBA). Mineral deposition was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT‐PCR. Expression and location of HMGB‐1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB‐1 expression, ERS and vascular calcification. However, inhibition of HMGB‐1 with Gly or inhibition of ERS with 4‐PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB‐1 attenuated advanced glycation end products (AGEs)‐induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB‐1 in VSMCs, which was reversed by 4‐PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB‐1 and AGEs. However, inhibition of ERS with 4‐PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB‐1. Thus, diabetes induced translocation and secretion of HMGB‐1 via ERS, which resulted in calcification in diabetic mice and in AGEs‐treated VSMCs.
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影响因子：
9.3
作者：
von Scholten, Bernt Johan;Reinhard, Henrik;Rossing, Peter
通讯作者：
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影响因子：
4
作者：
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影响因子：
1.9
作者：
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通讯作者：
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影响因子：
16.2
作者：
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DOI：
10.1016/j.jtcvs.2015.09.077
发表时间：
2016-01-01
影响因子：
6
作者：
Wang, Bo;Li, Fei;Dong, Nianguo
通讯作者：
Dong, Nianguo