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Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis

Acute kidney injury (AKI) and chronic kidney disease (CKD) represent different stages of renal failure; thus, CKD can be regarded as a result of AKI deterioration. Previous studies have demonstrated that immune cell infiltration, oxidative stress, and metabolic mentalism can support renal fibrosis p...

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Autores principales: Wu, Renyan, Li, Jiawei, Tu, Guowei, Su, Ying, Zhang, Xuepeng, Luo, Zhe, Rong, Ruiming, Zhang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586649/
https://www.ncbi.nlm.nih.gov/pubmed/34777334
http://dx.doi.org/10.3389/fimmu.2021.699192
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author Wu, Renyan
Li, Jiawei
Tu, Guowei
Su, Ying
Zhang, Xuepeng
Luo, Zhe
Rong, Ruiming
Zhang, Yi
author_facet Wu, Renyan
Li, Jiawei
Tu, Guowei
Su, Ying
Zhang, Xuepeng
Luo, Zhe
Rong, Ruiming
Zhang, Yi
author_sort Wu, Renyan
collection PubMed
description Acute kidney injury (AKI) and chronic kidney disease (CKD) represent different stages of renal failure; thus, CKD can be regarded as a result of AKI deterioration. Previous studies have demonstrated that immune cell infiltration, oxidative stress, and metabolic mentalism can support renal fibrosis progression in AKI cases. However, the most important triggers and cell types involved in this pathological progression remain unclear. This study was conducted to shed light into the underlying cellular and molecular features of renal fibrosis progression through the analysis of three mouse whole kidney and one human single-cell RNA-sequencing datasets publicly available. According to the different causes of AKI (ischemia reperfusion injury [IRI] or cisplatin), the mouse samples were divided into the CIU [control-IRI-unilateral ureteral obstruction (UUO)] and CCU (control-cisplatin-UUO) groups. Comparisons between groups revealed eight different modules of differentially expressed genes (DEGs). A total of 1,214 genes showed the same expression pattern in both CIU and CCU groups; however, 1,816 and 1,308 genes were expressed specifically in the CCU and CIU groups, respectively. Further assessment of the DEGs according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway and Gene Ontology (GO) showed that T-cell activation, fatty acid metabolic process, and arachidonic acid metabolism were involved in the fibrosis progression in CIU and CCU. Single-cell RNA-sequencing data along with the collected DEGs information also revealed that the T-cell activation mainly happened in immune cells, whereas the fatty acid metabolic process and arachidonic acid metabolism occurred in tubule cells. Taken together, these findings suggest that the fibrosis process differed between the CIU and CCU stages, in which immune and tubule cells have different functions. These identified cellular and molecular features of the different stages of fibrosis progression may pave the way for exploring novel potential therapeutic strategies in the clinic.
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spelling pubmed-85866492021-11-13 Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis Wu, Renyan Li, Jiawei Tu, Guowei Su, Ying Zhang, Xuepeng Luo, Zhe Rong, Ruiming Zhang, Yi Front Immunol Immunology Acute kidney injury (AKI) and chronic kidney disease (CKD) represent different stages of renal failure; thus, CKD can be regarded as a result of AKI deterioration. Previous studies have demonstrated that immune cell infiltration, oxidative stress, and metabolic mentalism can support renal fibrosis progression in AKI cases. However, the most important triggers and cell types involved in this pathological progression remain unclear. This study was conducted to shed light into the underlying cellular and molecular features of renal fibrosis progression through the analysis of three mouse whole kidney and one human single-cell RNA-sequencing datasets publicly available. According to the different causes of AKI (ischemia reperfusion injury [IRI] or cisplatin), the mouse samples were divided into the CIU [control-IRI-unilateral ureteral obstruction (UUO)] and CCU (control-cisplatin-UUO) groups. Comparisons between groups revealed eight different modules of differentially expressed genes (DEGs). A total of 1,214 genes showed the same expression pattern in both CIU and CCU groups; however, 1,816 and 1,308 genes were expressed specifically in the CCU and CIU groups, respectively. Further assessment of the DEGs according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway and Gene Ontology (GO) showed that T-cell activation, fatty acid metabolic process, and arachidonic acid metabolism were involved in the fibrosis progression in CIU and CCU. Single-cell RNA-sequencing data along with the collected DEGs information also revealed that the T-cell activation mainly happened in immune cells, whereas the fatty acid metabolic process and arachidonic acid metabolism occurred in tubule cells. Taken together, these findings suggest that the fibrosis process differed between the CIU and CCU stages, in which immune and tubule cells have different functions. These identified cellular and molecular features of the different stages of fibrosis progression may pave the way for exploring novel potential therapeutic strategies in the clinic. Frontiers Media S.A. 2021-10-29 /pmc/articles/PMC8586649/ /pubmed/34777334 http://dx.doi.org/10.3389/fimmu.2021.699192 Text en Copyright © 2021 Wu, Li, Tu, Su, Zhang, Luo, Rong and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wu, Renyan
Li, Jiawei
Tu, Guowei
Su, Ying
Zhang, Xuepeng
Luo, Zhe
Rong, Ruiming
Zhang, Yi
Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis
title Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis
title_full Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis
title_fullStr Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis
title_full_unstemmed Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis
title_short Comprehensive Molecular and Cellular Characterization of Acute Kidney Injury Progression to Renal Fibrosis
title_sort comprehensive molecular and cellular characterization of acute kidney injury progression to renal fibrosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586649/
https://www.ncbi.nlm.nih.gov/pubmed/34777334
http://dx.doi.org/10.3389/fimmu.2021.699192
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