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Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular...

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Autores principales: Wu, Hao Jia, Yiu, Wai Han, Li, Rui Xi, Wong, Dickson W. L., Leung, Joseph C. K., Chan, Loretta Y. Y., Zhang, Yuelin, Lian, Qizhou, Lin, Miao, Tse, Hung Fat, Lai, Kar Neng, Tang, Sydney C. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960109/
https://www.ncbi.nlm.nih.gov/pubmed/24646687
http://dx.doi.org/10.1371/journal.pone.0090883
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author Wu, Hao Jia
Yiu, Wai Han
Li, Rui Xi
Wong, Dickson W. L.
Leung, Joseph C. K.
Chan, Loretta Y. Y.
Zhang, Yuelin
Lian, Qizhou
Lin, Miao
Tse, Hung Fat
Lai, Kar Neng
Tang, Sydney C. W.
author_facet Wu, Hao Jia
Yiu, Wai Han
Li, Rui Xi
Wong, Dickson W. L.
Leung, Joseph C. K.
Chan, Loretta Y. Y.
Zhang, Yuelin
Lian, Qizhou
Lin, Miao
Tse, Hung Fat
Lai, Kar Neng
Tang, Sydney C. W.
author_sort Wu, Hao Jia
collection PubMed
description Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.
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spelling pubmed-39601092014-03-24 Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis Wu, Hao Jia Yiu, Wai Han Li, Rui Xi Wong, Dickson W. L. Leung, Joseph C. K. Chan, Loretta Y. Y. Zhang, Yuelin Lian, Qizhou Lin, Miao Tse, Hung Fat Lai, Kar Neng Tang, Sydney C. W. PLoS One Research Article Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6. Public Library of Science 2014-03-19 /pmc/articles/PMC3960109/ /pubmed/24646687 http://dx.doi.org/10.1371/journal.pone.0090883 Text en © 2014 Wu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wu, Hao Jia
Yiu, Wai Han
Li, Rui Xi
Wong, Dickson W. L.
Leung, Joseph C. K.
Chan, Loretta Y. Y.
Zhang, Yuelin
Lian, Qizhou
Lin, Miao
Tse, Hung Fat
Lai, Kar Neng
Tang, Sydney C. W.
Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis
title Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis
title_full Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis
title_fullStr Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis
title_full_unstemmed Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis
title_short Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis
title_sort mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960109/
https://www.ncbi.nlm.nih.gov/pubmed/24646687
http://dx.doi.org/10.1371/journal.pone.0090883
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