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Updated: Nov 9, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Bone marrow mesenchymal stem cell exosomes suppress phosphate-induced aortic calcification via SIRT6-HMGB1
Wenqian Wei1, Xiaodong Guo2, Lijie Gu1
1Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Rd, Hongkou District, Shanghai, 200080, China.
Insights
Bone marrow mesenchymal stem cell-derived exosomes inhibit vascular calcification in chronic kidney disease (CKD) by regulating Sirtuin 6 (SIRT6) and high mobility group box 1 (HMGB1) deacetylation, improving renal function.
Area of Science:
- Nephrology
- Vascular Biology
- Stem Cell Therapy
Background:
- Vascular calcification in chronic kidney disease (CKD) is a significant mortality risk factor.
- Elevated high mobility group box 1 (HMGB1) drives vascular calcification in CKD via the Wnt/β-catenin pathway.
- Sirtuin 6 (SIRT6) mitigates CKD fibrosis by inhibiting β-catenin target gene expression through deacetylation.
Purpose of the Study:
- Investigate if bone marrow mesenchymal stem cell (BMSC)-derived exosomes inhibit vascular calcification in CKD.
- Determine the role of SIRT6 activity in this inhibition.
- Assess the regulatory relationship between HMGB1 and SIRT6 in this context.
Main Methods:
- Utilized a 5/6 nephrectomized mouse model of CKD fed a high-phosphate diet to induce aortic calcification.
- Measured CKD characteristics, osteogenic markers, and calcium deposition.
- Performed in vitro assays to validate in vivo findings, including HMGB1 and SIRT6 expression analysis.
Main Results:
- High phosphate induced HMGB1 nuclear-to-cytosol translocation and expression of osteogenic genes (Runx2, osteopontin, Msx2).
- BMSC-derived exosomes attenuated CKD-related fibrosis and osteogenic gene induction, with reduced efficacy upon SIRT6 suppression.
- SIRT6 deacetylated and modulated HMGB1 cytosol translocation in vascular smooth muscle cells.
Conclusions:
- BMSC-derived exosomes effectively inhibit high phosphate-induced aortic calcification in CKD.
- The mechanism involves the SIRT6-HMGB1 deacetylation pathway.
- Exosome treatment ameliorates renal function in this CKD model.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
Our results indicate that BMSC-derived exosomes inhibit high phosphate-induced aortic calcification and ameliorate renal function via the SIRT6-HMGB1 deacetylation pathway.
