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Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury
Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia re...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036000/ https://www.ncbi.nlm.nih.gov/pubmed/35112806 http://dx.doi.org/10.1002/advs.202103675 |
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author | Yao, Weijian Chen, Ying Li, Zehua Ji, Jing You, Abin Jin, Shanzhao Ma, Yuan Zhao, Youlu Wang, Jinwei Qu, Lei Wang, Hui Xiang, Chengang Wang, Suxia Liu, Gang Bai, Fan Yang, Li |
author_facet | Yao, Weijian Chen, Ying Li, Zehua Ji, Jing You, Abin Jin, Shanzhao Ma, Yuan Zhao, Youlu Wang, Jinwei Qu, Lei Wang, Hui Xiang, Chengang Wang, Suxia Liu, Gang Bai, Fan Yang, Li |
author_sort | Yao, Weijian |
collection | PubMed |
description | Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia reperfusion injury induced AKI (IRI‐AKI) remains unclear. Using single‐cell RNA sequencing of the mononuclear phagocytic system in the murine IRI model, the authors demonstrate the complementary roles of kidney resident macrophages (KRMs) and monocyte‐derived infiltrated macrophages (IMs) in modulating tissue inflammation and promoting tissue repair. A unique population of S100a9(hi)Ly6c(hi) IMs is identified as an early responder to AKI, mediating the initiation and amplification of kidney inflammation. Kidney infiltration of S100A8/A9(+) macrophages and the relevance of renal S100A8/A9 to tissue injury is confirmed in human AKI. Targeting the S100a8/a9 signaling with small‐molecule inhibitors exhibits renal protective effects represented by improved renal function and reduced mortality in bilateral IRI model, and decreased inflammatory response, ameliorated kidney injury, and improved long‐term outcome with decreased renal fibrosis in the unilateral IRI model. The findings support S100A8/A9 blockade as a feasible and clinically relevant therapy potentially waiting for translation in human AKI. |
format | Online Article Text |
id | pubmed-9036000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90360002022-04-27 Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury Yao, Weijian Chen, Ying Li, Zehua Ji, Jing You, Abin Jin, Shanzhao Ma, Yuan Zhao, Youlu Wang, Jinwei Qu, Lei Wang, Hui Xiang, Chengang Wang, Suxia Liu, Gang Bai, Fan Yang, Li Adv Sci (Weinh) Research Articles Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia reperfusion injury induced AKI (IRI‐AKI) remains unclear. Using single‐cell RNA sequencing of the mononuclear phagocytic system in the murine IRI model, the authors demonstrate the complementary roles of kidney resident macrophages (KRMs) and monocyte‐derived infiltrated macrophages (IMs) in modulating tissue inflammation and promoting tissue repair. A unique population of S100a9(hi)Ly6c(hi) IMs is identified as an early responder to AKI, mediating the initiation and amplification of kidney inflammation. Kidney infiltration of S100A8/A9(+) macrophages and the relevance of renal S100A8/A9 to tissue injury is confirmed in human AKI. Targeting the S100a8/a9 signaling with small‐molecule inhibitors exhibits renal protective effects represented by improved renal function and reduced mortality in bilateral IRI model, and decreased inflammatory response, ameliorated kidney injury, and improved long‐term outcome with decreased renal fibrosis in the unilateral IRI model. The findings support S100A8/A9 blockade as a feasible and clinically relevant therapy potentially waiting for translation in human AKI. John Wiley and Sons Inc. 2022-02-03 /pmc/articles/PMC9036000/ /pubmed/35112806 http://dx.doi.org/10.1002/advs.202103675 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Yao, Weijian Chen, Ying Li, Zehua Ji, Jing You, Abin Jin, Shanzhao Ma, Yuan Zhao, Youlu Wang, Jinwei Qu, Lei Wang, Hui Xiang, Chengang Wang, Suxia Liu, Gang Bai, Fan Yang, Li Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury |
title | Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury |
title_full | Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury |
title_fullStr | Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury |
title_full_unstemmed | Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury |
title_short | Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury |
title_sort | single cell rna sequencing identifies a unique inflammatory macrophage subset as a druggable target for alleviating acute kidney injury |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036000/ https://www.ncbi.nlm.nih.gov/pubmed/35112806 http://dx.doi.org/10.1002/advs.202103675 |
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