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

doi:10.3390/cells12010161

Open AccessArticle

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

by

Qing Li

,

Cailin Zhang

,

Jia Shi

,

Yi Yang

,

Xue Xing

,

Yanan Wang

,

Xiaona Zhan

,

Le Wang

,

Gang Xu

^*,† and

Fan He

^*,†

Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2023, 12(1), 161; https://doi.org/10.3390/cells12010161

Submission received: 26 November 2022 / Revised: 18 December 2022 / Accepted: 29 December 2022 / Published: 30 December 2022

(This article belongs to the Section Autophagy)

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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.

Keywords: vascular calcification; macrophage; exosome; CKD; TGFBR1; let-7b-5p

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MDPI and ACS Style

Li, Q.; Zhang, C.; Shi, J.; Yang, Y.; Xing, X.; Wang, Y.; Zhan, X.; Wang, L.; Xu, G.; He, F. High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease. Cells 2023, 12, 161. https://doi.org/10.3390/cells12010161

AMA Style

Li Q, Zhang C, Shi J, Yang Y, Xing X, Wang Y, Zhan X, Wang L, Xu G, He F. High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease. Cells. 2023; 12(1):161. https://doi.org/10.3390/cells12010161

Chicago/Turabian Style

Li, Qing, Cailin Zhang, Jia Shi, Yi Yang, Xue Xing, Yanan Wang, Xiaona Zhan, Le Wang, Gang Xu, and Fan He. 2023. "High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease" Cells 12, no. 1: 161. https://doi.org/10.3390/cells12010161

APA Style

Li, Q., Zhang, C., Shi, J., Yang, Y., Xing, X., Wang, Y., Zhan, X., Wang, L., Xu, G., & He, F. (2023). High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease. Cells, 12(1), 161. https://doi.org/10.3390/cells12010161

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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

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