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Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model

Phagocytosis is an inherent function of tissue macrophages for the removal of apoptotic cells and cellular debris during acute and chronic injury; however, the dynamics of this event during fibrosis development is unknown. We aim to prove that during the development of kidney fibrosis in the unilate...

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Autores principales: Calle, Priscila, Játiva, Soraya, Torrico, Selene, Muñoz, Angeles, García, Miriam, Sola, Anna, Serra, Dolors, Mera, Paula, Herrero, Laura, Hotter, Georgina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304788/
https://www.ncbi.nlm.nih.gov/pubmed/34209378
http://dx.doi.org/10.3390/cells10071650
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author Calle, Priscila
Játiva, Soraya
Torrico, Selene
Muñoz, Angeles
García, Miriam
Sola, Anna
Serra, Dolors
Mera, Paula
Herrero, Laura
Hotter, Georgina
author_facet Calle, Priscila
Játiva, Soraya
Torrico, Selene
Muñoz, Angeles
García, Miriam
Sola, Anna
Serra, Dolors
Mera, Paula
Herrero, Laura
Hotter, Georgina
author_sort Calle, Priscila
collection PubMed
description Phagocytosis is an inherent function of tissue macrophages for the removal of apoptotic cells and cellular debris during acute and chronic injury; however, the dynamics of this event during fibrosis development is unknown. We aim to prove that during the development of kidney fibrosis in the unilateral ureteral obstruction (UUO) model, there are some populations of macrophage with a reduced ability to phagocytose, and whether the infusion of a population of phagocytic macrophages could reduce fibrosis in the murine model UUO. For this purpose, we have identified the macrophage populations during the development of fibrosis and have characterized their phagocytic ability and their expression of CPT1a. Furthermore, we have evaluated the therapeutic effect of macrophages overexpressing CPT1a with high phagocytic skills. We evidenced that the macrophage population which exhibits high phagocytic ability (F4/80low-CD11b) in fibrotic animals decreases during the progression of fibrosis while the macrophage population with lower phagocytic ability (F4/80high-CD11b) in fibrotic conditions, conversely, increases and CPT1a macrophage cell therapy with a strengthening phagocytic ability is associated with a therapeutic effect on kidney fibrosis. We have developed a therapeutic approach to reduce fibrosis in the UUO model by enrichment of the kidney resident macrophage population with a higher proportion of exogenous phagocytic macrophages overexpressing CPT1a.
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spelling pubmed-83047882021-07-25 Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model Calle, Priscila Játiva, Soraya Torrico, Selene Muñoz, Angeles García, Miriam Sola, Anna Serra, Dolors Mera, Paula Herrero, Laura Hotter, Georgina Cells Article Phagocytosis is an inherent function of tissue macrophages for the removal of apoptotic cells and cellular debris during acute and chronic injury; however, the dynamics of this event during fibrosis development is unknown. We aim to prove that during the development of kidney fibrosis in the unilateral ureteral obstruction (UUO) model, there are some populations of macrophage with a reduced ability to phagocytose, and whether the infusion of a population of phagocytic macrophages could reduce fibrosis in the murine model UUO. For this purpose, we have identified the macrophage populations during the development of fibrosis and have characterized their phagocytic ability and their expression of CPT1a. Furthermore, we have evaluated the therapeutic effect of macrophages overexpressing CPT1a with high phagocytic skills. We evidenced that the macrophage population which exhibits high phagocytic ability (F4/80low-CD11b) in fibrotic animals decreases during the progression of fibrosis while the macrophage population with lower phagocytic ability (F4/80high-CD11b) in fibrotic conditions, conversely, increases and CPT1a macrophage cell therapy with a strengthening phagocytic ability is associated with a therapeutic effect on kidney fibrosis. We have developed a therapeutic approach to reduce fibrosis in the UUO model by enrichment of the kidney resident macrophage population with a higher proportion of exogenous phagocytic macrophages overexpressing CPT1a. MDPI 2021-06-30 /pmc/articles/PMC8304788/ /pubmed/34209378 http://dx.doi.org/10.3390/cells10071650 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Calle, Priscila
Játiva, Soraya
Torrico, Selene
Muñoz, Angeles
García, Miriam
Sola, Anna
Serra, Dolors
Mera, Paula
Herrero, Laura
Hotter, Georgina
Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
title Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
title_full Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
title_fullStr Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
title_full_unstemmed Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
title_short Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
title_sort infusion of phagocytic macrophages overexpressing cpt1a ameliorates kidney fibrosis in the uuo model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304788/
https://www.ncbi.nlm.nih.gov/pubmed/34209378
http://dx.doi.org/10.3390/cells10071650
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