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Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis
Interstitial fibrosis is a common feature of chronic kidney disease, and platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells are reportedly the major source of scar-producing myofibroblasts. We had previously demonstrated that albumin and its derivative R-III (a retinol-bi...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603238/ https://www.ncbi.nlm.nih.gov/pubmed/33086608 http://dx.doi.org/10.3390/biomedicines8100431 |
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author | Cha, Jin Joo Mandal, Chanchal Ghee, Jung Yeon Yoo, Ji Ae Lee, Mi Jin Kang, Young Sun Hyun, Young Youl Lee, Ji Eun Kim, Hyun Wook Han, Sang Youb Han, Jee Young Chung, Ah Young Yoon, Dae Wui Rhyu, Im Joo Oh, Junseo Cha, Dae Ryong |
author_facet | Cha, Jin Joo Mandal, Chanchal Ghee, Jung Yeon Yoo, Ji Ae Lee, Mi Jin Kang, Young Sun Hyun, Young Youl Lee, Ji Eun Kim, Hyun Wook Han, Sang Youb Han, Jee Young Chung, Ah Young Yoon, Dae Wui Rhyu, Im Joo Oh, Junseo Cha, Dae Ryong |
author_sort | Cha, Jin Joo |
collection | PubMed |
description | Interstitial fibrosis is a common feature of chronic kidney disease, and platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells are reportedly the major source of scar-producing myofibroblasts. We had previously demonstrated that albumin and its derivative R-III (a retinol-binding protein-albumin domain III fusion protein) inhibited the transdifferentiation/activation of hepatic stellate cells (HSCs) to myofibroblasts and that R-III administration reduced liver fibrosis. In this study, we isolated cells (referred to as renal stellate cells, RSCs) from rat kidney tissues using the HSC isolation protocol and compared their morphological and biochemical characteristics with those of HSCs. RSCs shared many characteristics with HSCs, such as storage of vitamin A-containing lipid droplets and expression of HSC markers as well as pericyte markers. RSCs underwent spontaneous transdifferentiation into myofibroblasts in in vitro culture, which was inhibited by albumin expression or R-III treatment. We also evaluated the therapeutic effects of R-III in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Injected R-III localized predominantly in cytoglobin/stellate cell activation-associated protein (Cygb/STAP)-positive cells in the kidney and reduced renal fibrosis. These findings suggest that RSCs can be recognized as the renal counterparts of HSCs and that RSCs represent an attractive therapeutic target for anti-fibrotic therapy. |
format | Online Article Text |
id | pubmed-7603238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76032382020-11-01 Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis Cha, Jin Joo Mandal, Chanchal Ghee, Jung Yeon Yoo, Ji Ae Lee, Mi Jin Kang, Young Sun Hyun, Young Youl Lee, Ji Eun Kim, Hyun Wook Han, Sang Youb Han, Jee Young Chung, Ah Young Yoon, Dae Wui Rhyu, Im Joo Oh, Junseo Cha, Dae Ryong Biomedicines Article Interstitial fibrosis is a common feature of chronic kidney disease, and platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells are reportedly the major source of scar-producing myofibroblasts. We had previously demonstrated that albumin and its derivative R-III (a retinol-binding protein-albumin domain III fusion protein) inhibited the transdifferentiation/activation of hepatic stellate cells (HSCs) to myofibroblasts and that R-III administration reduced liver fibrosis. In this study, we isolated cells (referred to as renal stellate cells, RSCs) from rat kidney tissues using the HSC isolation protocol and compared their morphological and biochemical characteristics with those of HSCs. RSCs shared many characteristics with HSCs, such as storage of vitamin A-containing lipid droplets and expression of HSC markers as well as pericyte markers. RSCs underwent spontaneous transdifferentiation into myofibroblasts in in vitro culture, which was inhibited by albumin expression or R-III treatment. We also evaluated the therapeutic effects of R-III in unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Injected R-III localized predominantly in cytoglobin/stellate cell activation-associated protein (Cygb/STAP)-positive cells in the kidney and reduced renal fibrosis. These findings suggest that RSCs can be recognized as the renal counterparts of HSCs and that RSCs represent an attractive therapeutic target for anti-fibrotic therapy. MDPI 2020-10-19 /pmc/articles/PMC7603238/ /pubmed/33086608 http://dx.doi.org/10.3390/biomedicines8100431 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cha, Jin Joo Mandal, Chanchal Ghee, Jung Yeon Yoo, Ji Ae Lee, Mi Jin Kang, Young Sun Hyun, Young Youl Lee, Ji Eun Kim, Hyun Wook Han, Sang Youb Han, Jee Young Chung, Ah Young Yoon, Dae Wui Rhyu, Im Joo Oh, Junseo Cha, Dae Ryong Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis |
title | Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis |
title_full | Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis |
title_fullStr | Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis |
title_full_unstemmed | Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis |
title_short | Inhibition of Renal Stellate Cell Activation Reduces Renal Fibrosis |
title_sort | inhibition of renal stellate cell activation reduces renal fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603238/ https://www.ncbi.nlm.nih.gov/pubmed/33086608 http://dx.doi.org/10.3390/biomedicines8100431 |
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