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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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.
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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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