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Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6

BACKGROUND: Life-long peritoneal dialysis (PD) as a renal replacement therapy is limited by peritoneal fibrosis. Previous studies showed immunomodulatory and antifibrotic effects of adipose-derived mesenchymal stem cells (ADSCs) on peritoneal fibrosis. However, the role of the peritoneal macrophage...

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Autores principales: Yang, Chih-Yu, Chang, Pu-Yuan, Chen, Jun-Yi, Wu, Bo-Sheng, Yang, An-Hang, Lee, Oscar Kuang-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977319/
https://www.ncbi.nlm.nih.gov/pubmed/33741073
http://dx.doi.org/10.1186/s13287-021-02270-4
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author Yang, Chih-Yu
Chang, Pu-Yuan
Chen, Jun-Yi
Wu, Bo-Sheng
Yang, An-Hang
Lee, Oscar Kuang-Sheng
author_facet Yang, Chih-Yu
Chang, Pu-Yuan
Chen, Jun-Yi
Wu, Bo-Sheng
Yang, An-Hang
Lee, Oscar Kuang-Sheng
author_sort Yang, Chih-Yu
collection PubMed
description BACKGROUND: Life-long peritoneal dialysis (PD) as a renal replacement therapy is limited by peritoneal fibrosis. Previous studies showed immunomodulatory and antifibrotic effects of adipose-derived mesenchymal stem cells (ADSCs) on peritoneal fibrosis. However, the role of the peritoneal macrophage in this process remains uninvestigated. METHODS: We examined the therapeutic effects of ADSC and bone marrow-derived mesenchymal stem cells (BM-MSC) in the rat model of dialysis-induced peritoneal fibrosis using methylglyoxal. In addition, treatment of macrophages with the conditioned medium of ADSC and BM-MSC was performed individually to identify the beneficial component of the stem cell secretome. RESULTS: In the in vivo experiments, we found dialysis-induced rat peritoneal fibrosis was attenuated by both ADSC and BM-MSC. Interestingly, ADSC possessed a more prominent therapeutic effect than BM-MSC in ameliorating peritoneal membrane thickening while also upregulating epithelial cell markers in rat peritoneal tissues. The therapeutic effects of ADSC were positively associated with M2 macrophage polarization. In the in vitro experiments, we confirmed that interleukin-6 (IL-6) secreted by MSCs upon transforming growth factor-β1 stimulation promotes M2 macrophage polarization. CONCLUSIONS: In dialysis-induced peritoneal fibrosis, MSCs are situated in an inflammatory environment of TGF-β1 and secrete IL-6 to polarize macrophages into the M2 phenotype. Our findings reveal a previously unidentified role of tissue macrophage in this antifibrotic process. ADSC has the advantage of abundance and accessibility, making the application values extremely promising. GRAPHICAL ABSTRACT: In dialysis-induced peritoneal fibrosis, peritoneal mesothelial cells secrete transforming growth factor-β1 (TGF-β1) when exposed to methylglyoxal (MGO)-containing peritoneal dialysate. When situated in TGF-β1, the inflammatory environment induces mesenchymal stem cells to secrete interleukin-6 (IL-6), IL-6 polarizes macrophages into the M2 phenotype. The dominant peritoneal tissue M2 macrophages, marked by upregulated Arg-1 expression, account for the attenuation of MGO-induced dedifferentiation of peritoneal mesothelial cells to maintain epithelial integrity. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02270-4.
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spelling pubmed-79773192021-03-22 Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6 Yang, Chih-Yu Chang, Pu-Yuan Chen, Jun-Yi Wu, Bo-Sheng Yang, An-Hang Lee, Oscar Kuang-Sheng Stem Cell Res Ther Research BACKGROUND: Life-long peritoneal dialysis (PD) as a renal replacement therapy is limited by peritoneal fibrosis. Previous studies showed immunomodulatory and antifibrotic effects of adipose-derived mesenchymal stem cells (ADSCs) on peritoneal fibrosis. However, the role of the peritoneal macrophage in this process remains uninvestigated. METHODS: We examined the therapeutic effects of ADSC and bone marrow-derived mesenchymal stem cells (BM-MSC) in the rat model of dialysis-induced peritoneal fibrosis using methylglyoxal. In addition, treatment of macrophages with the conditioned medium of ADSC and BM-MSC was performed individually to identify the beneficial component of the stem cell secretome. RESULTS: In the in vivo experiments, we found dialysis-induced rat peritoneal fibrosis was attenuated by both ADSC and BM-MSC. Interestingly, ADSC possessed a more prominent therapeutic effect than BM-MSC in ameliorating peritoneal membrane thickening while also upregulating epithelial cell markers in rat peritoneal tissues. The therapeutic effects of ADSC were positively associated with M2 macrophage polarization. In the in vitro experiments, we confirmed that interleukin-6 (IL-6) secreted by MSCs upon transforming growth factor-β1 stimulation promotes M2 macrophage polarization. CONCLUSIONS: In dialysis-induced peritoneal fibrosis, MSCs are situated in an inflammatory environment of TGF-β1 and secrete IL-6 to polarize macrophages into the M2 phenotype. Our findings reveal a previously unidentified role of tissue macrophage in this antifibrotic process. ADSC has the advantage of abundance and accessibility, making the application values extremely promising. GRAPHICAL ABSTRACT: In dialysis-induced peritoneal fibrosis, peritoneal mesothelial cells secrete transforming growth factor-β1 (TGF-β1) when exposed to methylglyoxal (MGO)-containing peritoneal dialysate. When situated in TGF-β1, the inflammatory environment induces mesenchymal stem cells to secrete interleukin-6 (IL-6), IL-6 polarizes macrophages into the M2 phenotype. The dominant peritoneal tissue M2 macrophages, marked by upregulated Arg-1 expression, account for the attenuation of MGO-induced dedifferentiation of peritoneal mesothelial cells to maintain epithelial integrity. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02270-4. BioMed Central 2021-03-19 /pmc/articles/PMC7977319/ /pubmed/33741073 http://dx.doi.org/10.1186/s13287-021-02270-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yang, Chih-Yu
Chang, Pu-Yuan
Chen, Jun-Yi
Wu, Bo-Sheng
Yang, An-Hang
Lee, Oscar Kuang-Sheng
Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
title Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
title_full Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
title_fullStr Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
title_full_unstemmed Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
title_short Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
title_sort adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977319/
https://www.ncbi.nlm.nih.gov/pubmed/33741073
http://dx.doi.org/10.1186/s13287-021-02270-4
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