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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
High Mobility Group Box 1 Promotes Aortic Calcification in Chronic Kidney Disease via the Wnt/β-Catenin Pathway
Xiucai Jin1, Shu Rong2, Weijie Yuan2
1Department of Ultrasound, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
Insights
High-mobility group box 1 (HMGB1) protein is linked to vascular calcification in chronic kidney disease (CKD). Reducing HMGB1 may improve kidney and vascular function in CKD patients.
Area of Science:
- Nephrology
- Cardiovascular Biology
- Molecular Medicine
Background:
- Vascular calcification (VC) is a significant complication in chronic kidney disease (CKD), contributing to high cardiovascular mortality.
- High phosphate levels exacerbate VC and renal dysfunction in CKD.
- The role of high-mobility group box 1 (HMGB1) in CKD-associated VC requires further elucidation.
Purpose of the Study:
- To investigate the role of HMGB1 in high phosphate-induced vascular calcification and renal dysfunction in a mouse model of CKD.
- To explore the underlying molecular mechanisms involving HMGB1 and β-catenin in VC.
Main Methods:
- Utilized a 5/6 nephrectomy mouse model of CKD with high phosphate administration.
- Measured serum HMGB1 levels and kidney function markers in CKD patients and mice using ELISA.
- Analyzed aortic calcification via immunofluorescence and Alizarin red staining.
- Assessed protein expression changes following HMGB1 or β-catenin silencing using western blotting.
Main Results:
- Serum HMGB1 levels were elevated in CKD patients and correlated with disease severity.
- High phosphate induced HMGB1 translocation and aortic calcification in CKD mice.
- HMGB1 knockdown partially improved renal and vascular function.
- Silencing β-catenin reversed high phosphate-induced calcification and improved renal markers.
Conclusions:
- HMGB1 plays a critical role in vascular calcification associated with chronic kidney disease.
- The HMGB1-mediated pathway, involving β-catenin, contributes to VC in CKD.
- Targeting HMGB1 may offer a therapeutic strategy for managing VC in CKD.
Abstract:
Vascular calcification (VC) is common in chronic kidney disease (CKD), where cardiovascular mortality remains the leading cause of death. Here, we examined the role of high-mobility group box1 (HMGB1), a nuclear DNA-binding protein involved in inflammation, in aortic calcification and renal dysfunction induced by high phosphate in a mouse model of CKD induced by 5/6 nephrectomy. HMGB1 and kidney function markers were measured by ELISA in the serum of CKD patients and in CKD mice. Sections of the aortas of mice were analyzed by immunofluorescence and Alizarin red staining, and protein lysates were generated to analyze the expression of related proteins in response to silencing of HMGB1 or β-catenin by western blotting. Our results showed that serum HMGB1 levels were significantly higher in CKD patients than in healthy controls and related to disease stage. High phosphate promoted the translocation of HMGB1 from the nucleus to the cytosol and aortic calcification in CKD mice in vivo, whereas HMGB1 knockdown ameliorated part of renal and vascular function. β-catenin silencing reversed high phosphate-induced calcification and restored renal marker levels. Taken together, our results suggest that HMGB1 is involved in VC associated with CKD via a mechanism involving the β-catenin.
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