Bone marrow mesenchymal stem cell exosomes suppress phosphate-induced aortic calcification via SIRT6-HMGB1 deacetylation.
Bone marrow mesenchymal stem cell exosomes suppress phosphate-induced aortic calcification via SIRT6-HMGB1 deacetylation.
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骨髓间充质干细胞外泌体通过SIRT 6-HMGB 1去乙酰化抑制磷酸盐诱导的主动脉钙化
DOI：
10.1186/s13287-021-02307-8
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发表时间：
2021-04-13
影响因子：
7.5
通讯作者：
Rong S
中科院分区：
文献类型：
--
作者：
Wei W;Guo X;Gu L;Jia J;Yang M;Yuan W;Rong S
Vascular calcification associated with chronic kidney disease (CKD) can increase the risk of mortality. Elevated serum levels of high mobility group box 1 (HMGB1) promotes vascular calcification in CKD via the Wnt/β-catenin pathway. Sirtuin 6 (SIRT6) prevents fibrosis in CKD by blocking the expression of β-catenin target genes through deacetylation. This study aimed to investigate whether the inhibition of vascular calcification by bone marrow mesenchymal stem cell (BMSC)-derived exosomes is related to SIRT6 activity and assess the regulatory relationship between HMGB1 and SIRT6. CKD characteristics, osteogenic markers, calcium deposition, and the differential expression of HMGB1 and SIRT6 have been measured in a 5/6 nephrectomized mouse CKD model fed a high-phosphate diet to induce aortic calcification. In vitro assays were also performed to validate the in vivo findings. High phosphate promotes the translocation of HMGB1 from the nucleus to the cytosol and induces the expression of Runx2, osteopontin, and Msx2. However, BMSC-derived exosomes were found to alleviate CKD-related fibrosis and the induction of osteogenic genes although less significantly when SIRT6 expression is suppressed. SIRT6 was found to modulate the cytosol translocation of HMGB1 by deacetylation in vascular smooth muscle cells. Our results indicate that BMSC-derived exosomes inhibit high phosphate-induced aortic calcification and ameliorate renal function via the SIRT6–HMGB1 deacetylation pathway.
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影响因子：
3.6
作者：
Mackenzie, N. C. W.;Staines, K. A.;Zhu, D.;Genever, P.;MacRae, V. E.
通讯作者：
MacRae, V. E.
影响因子：
19.6
作者：
通讯作者：
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WNT/β-连环蛋白信号通过直接调节 Runx2 基因表达促进 VSMC 成骨转分化和钙化
影响因子：
3.7
作者：
Cai, Ting;Sun, Danqin;He, Weichun
通讯作者：
He, Weichun
影响因子：
5.5
作者：
Villa-Bellosta, Ricardo;Millan, Angel;Sorribas, Victor
通讯作者：
Sorribas, Victor
影响因子：
5
作者：
Song, Yan;Hou, Menglin;Lu, Lihe
通讯作者：
Lu, Lihe