Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease

Acute kidney injury (AKI) substantially increases the risk of developing and worsening chronic kidney disease (CKD). The shift from AKI to CKD is a complex process that involves various cell types, with macrophages playing a key role in responding to renal injury. M1 and M2 macrophages—the two main...

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Main Authors: Xiaoqin Gao, Xingwei Liu, Zhaodi Han, Hui Liao, Rongshan Li
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2482121
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author Xiaoqin Gao
Xingwei Liu
Zhaodi Han
Hui Liao
Rongshan Li
author_facet Xiaoqin Gao
Xingwei Liu
Zhaodi Han
Hui Liao
Rongshan Li
author_sort Xiaoqin Gao
collection DOAJ
description Acute kidney injury (AKI) substantially increases the risk of developing and worsening chronic kidney disease (CKD). The shift from AKI to CKD is a complex process that involves various cell types, with macrophages playing a key role in responding to renal injury. M1 and M2 macrophages—the two main types of macrophages—have distinct functions at various stages. M1 macrophages induce kidney damage by secreting pro-inflammatory cytokines immediately after injury, whereas M2 macrophages subsequently facilitate kidney tissue repair. The conversion of macrophages from the M1 to M2 subtype is vital for effective repair after renal injury. However, when M2 macrophages infiltrate persistently, they can paradoxically cause fibrosis, thereby complicating recovery. As a key epigenetic regulatory factor, the deacetylase SIRT6 exerts various biological effects through its enzymatic reactions, including the regulation of cellular metabolism, antioxidant stress response, and inhibition of fibrosis. SIRT6 is expressed in all major types of renal resident cells and is demonstrated to protect the kidneys. SIRT6 promotes the transition from the M1 to M2 subtype; nevertheless, this process poses the risk of fibrosis if macrophages remain in the M2 subtype because of the influence of SIRT6. This review aimed (i) to delve into the intricate role of SIRT6 in macrophage polarization toward the M2 subtype in the context of the progression from AKI to CKD and (ii) to explore potential strategies that may effectively target and mitigate the progression from AKI to CKD.
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spelling doaj-art-7cf366a09f7e4ae5a89bdfb6d113b4f12025-08-20T02:24:33ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2482121Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney diseaseXiaoqin Gao0Xingwei Liu1Zhaodi Han2Hui Liao3Rongshan Li4Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDepartment of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDrug Clinical Trial Institution, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDrug Clinical Trial Institution, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDepartment of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaAcute kidney injury (AKI) substantially increases the risk of developing and worsening chronic kidney disease (CKD). The shift from AKI to CKD is a complex process that involves various cell types, with macrophages playing a key role in responding to renal injury. M1 and M2 macrophages—the two main types of macrophages—have distinct functions at various stages. M1 macrophages induce kidney damage by secreting pro-inflammatory cytokines immediately after injury, whereas M2 macrophages subsequently facilitate kidney tissue repair. The conversion of macrophages from the M1 to M2 subtype is vital for effective repair after renal injury. However, when M2 macrophages infiltrate persistently, they can paradoxically cause fibrosis, thereby complicating recovery. As a key epigenetic regulatory factor, the deacetylase SIRT6 exerts various biological effects through its enzymatic reactions, including the regulation of cellular metabolism, antioxidant stress response, and inhibition of fibrosis. SIRT6 is expressed in all major types of renal resident cells and is demonstrated to protect the kidneys. SIRT6 promotes the transition from the M1 to M2 subtype; nevertheless, this process poses the risk of fibrosis if macrophages remain in the M2 subtype because of the influence of SIRT6. This review aimed (i) to delve into the intricate role of SIRT6 in macrophage polarization toward the M2 subtype in the context of the progression from AKI to CKD and (ii) to explore potential strategies that may effectively target and mitigate the progression from AKI to CKD.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2482121Acute kidney injurychronic kidney diseasefibrosismacrophage polarizationSIRT6
spellingShingle Xiaoqin Gao
Xingwei Liu
Zhaodi Han
Hui Liao
Rongshan Li
Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease
Renal Failure
Acute kidney injury
chronic kidney disease
fibrosis
macrophage polarization
SIRT6
title Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease
title_full Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease
title_fullStr Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease
title_full_unstemmed Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease
title_short Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease
title_sort friend or foe the role of sirt6 on macrophage polarized to m2 subtype in acute kidney injury to chronic kidney disease
topic Acute kidney injury
chronic kidney disease
fibrosis
macrophage polarization
SIRT6
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2482121
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