The role of macrophages in renal fibrosis and therapeutic prospects

Monocytes/macrophages are the key regulators of tissue repair, regeneration, and fibrosis. Monocyte-derived macrophages, which are characterized by high heterogeneity and plasticity, are recruited, activated, and polarized throughout the process of renal fibrosis in response to the local microenviro...

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Main Authors: Di Niu, Jun Jie Yang, Dan Feng He
Format: Article
Language:English
Published: PeerJ Inc. 2025-07-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/19769.pdf
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author Di Niu
Jun Jie Yang
Dan Feng He
author_facet Di Niu
Jun Jie Yang
Dan Feng He
author_sort Di Niu
collection DOAJ
description Monocytes/macrophages are the key regulators of tissue repair, regeneration, and fibrosis. Monocyte-derived macrophages, which are characterized by high heterogeneity and plasticity, are recruited, activated, and polarized throughout the process of renal fibrosis in response to the local microenvironment. Increasing evidence suggests that phenotypic changes in macrophages are essential for chronic kidney disease (CKD) development and progression. Advanced bioinformatics and single-cell RNA sequencing analyses have revealed the critical mechanisms of macrophage iron homeostasis dysregulation and macrophage-to-myofibroblast transition (MMT), which may be a novel therapeutic target for renal fibrosis. In this review, we systematically examine the dynamic phenotype transitions of macrophages across distinct phases of kidney injury progression. Notably, we provide new insights into the multifaceted crosstalk between renal macrophages and neighboring parenchymal cells, including tubular epithelial cells, fibroblasts, podocytes, mesangial cells, and endothelial cells, mediated through diverse mechanisms, including soluble factors, extracellular vesicles, and direct cell-cell contact, and highlight the therapeutic potential of targeting macrophages.
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spelling doaj-art-237abb3fc13b48b992e250236fc0de8d2025-08-20T02:47:22ZengPeerJ Inc.PeerJ2167-83592025-07-0113e1976910.7717/peerj.19769The role of macrophages in renal fibrosis and therapeutic prospectsDi Niu0Jun Jie Yang1Dan Feng He2Department of Otolaryngology, The Eighth Hospital of Wuhan, Wuhan, ChinaDepartment of Pharmacy, The Eighth Hospital of Wuhan, Wuhan, ChinaDepartment of Pharmacy, The Eighth Hospital of Wuhan, Wuhan, ChinaMonocytes/macrophages are the key regulators of tissue repair, regeneration, and fibrosis. Monocyte-derived macrophages, which are characterized by high heterogeneity and plasticity, are recruited, activated, and polarized throughout the process of renal fibrosis in response to the local microenvironment. Increasing evidence suggests that phenotypic changes in macrophages are essential for chronic kidney disease (CKD) development and progression. Advanced bioinformatics and single-cell RNA sequencing analyses have revealed the critical mechanisms of macrophage iron homeostasis dysregulation and macrophage-to-myofibroblast transition (MMT), which may be a novel therapeutic target for renal fibrosis. In this review, we systematically examine the dynamic phenotype transitions of macrophages across distinct phases of kidney injury progression. Notably, we provide new insights into the multifaceted crosstalk between renal macrophages and neighboring parenchymal cells, including tubular epithelial cells, fibroblasts, podocytes, mesangial cells, and endothelial cells, mediated through diverse mechanisms, including soluble factors, extracellular vesicles, and direct cell-cell contact, and highlight the therapeutic potential of targeting macrophages.https://peerj.com/articles/19769.pdfCKDMacrophagesM1 and M2 phenotypesInterstitial fibrosisMMT
spellingShingle Di Niu
Jun Jie Yang
Dan Feng He
The role of macrophages in renal fibrosis and therapeutic prospects
PeerJ
CKD
Macrophages
M1 and M2 phenotypes
Interstitial fibrosis
MMT
title The role of macrophages in renal fibrosis and therapeutic prospects
title_full The role of macrophages in renal fibrosis and therapeutic prospects
title_fullStr The role of macrophages in renal fibrosis and therapeutic prospects
title_full_unstemmed The role of macrophages in renal fibrosis and therapeutic prospects
title_short The role of macrophages in renal fibrosis and therapeutic prospects
title_sort role of macrophages in renal fibrosis and therapeutic prospects
topic CKD
Macrophages
M1 and M2 phenotypes
Interstitial fibrosis
MMT
url https://peerj.com/articles/19769.pdf
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