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25-04-2024 | Chronic Kidney Disease | RESEARCH

Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis

Authors: Qitong Guo, Ping Li, Meiling Chen, Yihang Yu, Yonghong Wan, Zhaoxia Zhang, Chunnian Ren, Lianju Shen, Xing Liu, Dawei He, Yuanyuan Zhang, Guanghui Wei, Deying Zhang

Published in: Inflammation

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Abstract

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-β (TGF-β) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis.
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Literature
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go back to reference Liu, B., F. Ding, D. Hu, et al. 2018. Human umbilical cord mesenchymal stem cell conditioned medium attenuates renal fibrosis by reducing inflammation and epithelial-to-mesenchymal transition via the TLR4/NF-κB signaling pathway in vivo and in vitro [published correction appears in Stem Cell Res Ther. 2018 Mar 22;9(1):76]. Stem Cell Research and Therapy 9 (1): 7. https://doi.org/10.1186/s13287-017-0760-6.CrossRefPubMedPubMedCentral Liu, B., F. Ding, D. Hu, et al. 2018. Human umbilical cord mesenchymal stem cell conditioned medium attenuates renal fibrosis by reducing inflammation and epithelial-to-mesenchymal transition via the TLR4/NF-κB signaling pathway in vivo and in vitro [published correction appears in Stem Cell Res Ther. 2018 Mar 22;9(1):76]. Stem Cell Research and Therapy 9 (1): 7. https://​doi.​org/​10.​1186/​s13287-017-0760-6.CrossRefPubMedPubMedCentral
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go back to reference Qiu, Z., Z. Zhong, Y. Zhang, H. Tan, B. Deng, and G. Meng. 2022. Human umbilical cord mesenchymal stem cell-derived exosomal miR-335–5p attenuates the inflammation and tubular epithelial-myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels. Stem Cell Research & Therapy 13 (1): 373. https://doi.org/10.1186/s13287-022-03071-z.CrossRef Qiu, Z., Z. Zhong, Y. Zhang, H. Tan, B. Deng, and G. Meng. 2022. Human umbilical cord mesenchymal stem cell-derived exosomal miR-335–5p attenuates the inflammation and tubular epithelial-myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels. Stem Cell Research & Therapy 13 (1): 373. https://​doi.​org/​10.​1186/​s13287-022-03071-z.CrossRef
Metadata
Title
Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis
Authors
Qitong Guo
Ping Li
Meiling Chen
Yihang Yu
Yonghong Wan
Zhaoxia Zhang
Chunnian Ren
Lianju Shen
Xing Liu
Dawei He
Yuanyuan Zhang
Guanghui Wei
Deying Zhang
Publication date
25-04-2024
Publisher
Springer US
Published in
Inflammation
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-024-02027-0
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