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Updated: Aug 15, 2025
A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in
Qing Li1, Cailin Zhang1, Jia Shi1
1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Insights
Macrophage-derived exosomes promote vascular calcification in chronic kidney disease by suppressing let-7b-5p, upregulating TGFBR1, and activating SMAD3/RUNX2 signaling.
Area of Science:
- Cardiovascular Biology
- Renal Medicine
- Cell Biology
Background:
- Macrophage infiltration is linked to artery calcification in chronic kidney disease (CKD).
- The precise mechanisms by which macrophages drive vascular calcification (VC) progression are not fully understood.
- Understanding these mechanisms is crucial for developing targeted therapies for CKD-associated VC.
Purpose of the Study:
- To elucidate the role of macrophage-derived exosomes in promoting vascular calcification in high-phosphate conditions.
- To identify the specific molecular axis involved in this process.
- To explore potential therapeutic targets for CKD-associated VC.
Main Methods:
- Utilized miRNA-seq, RNA-seq, dual-luciferase reporter assay, and qRT-PCR.
- Employed CKD patient arteries and mouse models.
- Conducted gain-and-loss-of-function assays to validate molecular interactions.
Main Results:
- High-phosphate-stimulated macrophage-derived exosomes (Mexo-P) were found to suppress let-7b-5p expression in vascular smooth muscle cells (VSMCs).
- This suppression led to the upregulation of TGFBR1 in VSMCs.
- The let-7b-5p/TGFBR1 axis was confirmed to amplify SMAD3/RUNX2 signaling, driving VC progression.
Conclusions:
- Macrophage-derived exosomes promote CKD-associated vascular calcification via the let-7b-5p/TGFBR1 pathway under high-phosphate conditions.
- This pathway involves the amplification of SMAD3/RUNX2 signaling.
- Macrophages and their secreted exosomes represent potential therapeutic targets for managing vascular calcification in CKD.
Abstract:
Although macrophage infiltration has been proven to increase calcified artery media in chronic kidney disease (CKD) patients, the mechanism by which macrophages are involved in vascular calcification (VC) progression remains unclear. Taking advantage of miRNA-seq, RNA-seq, dual-luciferase reporter assay, qRT-PCR, and arteries from CKD patients as well as CKD mouse models, we identified that high-phosphate-stimulated macrophage-derived exosomes (Mexo-P) suppressed let-7b-5p expression in VSMCs, which further upregulated TGFBR1. Moreover, gain-and-loss-of-function assays were used to determine the regulatory effects and downstream mechanism of let-7b-5p and TGFBR1 on VC. Mechanically, Mexo-P induced VSMC TGFBR1 upregulation by suppressing let-7b-5p, which further amplifies SMAD3/RUNX2 signaling and thereby contributes to VC. Our findings indicate that macrophage-derived exosomes promote CKD-associated VC through the let-7b-5p/TGFBR1 axis in high-phosphate conditions. Our study provides insight into macrophages associated with VC, which might be potential therapeutical targets for VC.
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