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High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease

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 a...

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Autores principales: Li, Qing, Zhang, Cailin, Shi, Jia, Yang, Yi, Xing, Xue, Wang, Yanan, Zhan, Xiaona, Wang, Le, Xu, Gang, He, Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818696/
https://www.ncbi.nlm.nih.gov/pubmed/36611957
http://dx.doi.org/10.3390/cells12010161
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author Li, Qing
Zhang, Cailin
Shi, Jia
Yang, Yi
Xing, Xue
Wang, Yanan
Zhan, Xiaona
Wang, Le
Xu, Gang
He, Fan
author_facet Li, Qing
Zhang, Cailin
Shi, Jia
Yang, Yi
Xing, Xue
Wang, Yanan
Zhan, Xiaona
Wang, Le
Xu, Gang
He, Fan
author_sort Li, Qing
collection PubMed
description 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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spelling pubmed-98186962023-01-07 High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease Li, Qing Zhang, Cailin Shi, Jia Yang, Yi Xing, Xue Wang, Yanan Zhan, Xiaona Wang, Le Xu, Gang He, Fan Cells Article 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. MDPI 2022-12-30 /pmc/articles/PMC9818696/ /pubmed/36611957 http://dx.doi.org/10.3390/cells12010161 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Qing
Zhang, Cailin
Shi, Jia
Yang, Yi
Xing, Xue
Wang, Yanan
Zhan, Xiaona
Wang, Le
Xu, Gang
He, Fan
High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease
title High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease
title_full High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease
title_fullStr High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease
title_full_unstemmed High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease
title_short High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease
title_sort high-phosphate-stimulated macrophage-derived exosomes promote vascular calcification via let-7b-5p/tgfbr1 axis in chronic kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818696/
https://www.ncbi.nlm.nih.gov/pubmed/36611957
http://dx.doi.org/10.3390/cells12010161
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