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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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