Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition

AbstractClodronate liposomes are bisphosphonates encapsulated by liposomes that are known to induce macrophage depletion in vivo. In a previous study, clodronate liposomes improved renal ischemia/reperfusion (I/R) injury in mice, which may be due to effects on macrophage phenotypes. However, how inf...

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Main Authors: Zhizhi Hu, Juan Zhan, Guangchang Pei, Rui Zeng
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Renal Failure
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2022.2149412
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author Zhizhi Hu
Juan Zhan
Guangchang Pei
Rui Zeng
author_facet Zhizhi Hu
Juan Zhan
Guangchang Pei
Rui Zeng
author_sort Zhizhi Hu
collection DOAJ
description AbstractClodronate liposomes are bisphosphonates encapsulated by liposomes that are known to induce macrophage depletion in vivo. In a previous study, clodronate liposomes improved renal ischemia/reperfusion (I/R) injury in mice, which may be due to effects on macrophage phenotypes. However, how inflammatory cytokines secretion participates is unknown. In this study, we investigated the effect of macrophages in the I/R kidney by depleting macrophages with clodronate liposomes and changing inflammatory cytokines. C57BL/6 mice underwent I/R injury with or without clodronate liposomes administration on Days 5 and 15. Tubular injury, collagen deposition, and fibrosis were detected and analyzed by histological staining, immunocytochemistry (IHC), flow cytometry (FACS), and reverse transcription–polymerase chain reaction (RT–PCR). Inflammatory cytokines were detected and analyzed by Western blotting and RT–PCR. We found that clodronate liposomes alleviated renal fibrosis and tissue damage on both Days 5 and 15. KIM-1, IL-10, and TGF-β were reduced significantly in the clodronate liposomes treatment group. However, TNF-α was not different between the clodronate liposomes treatment group and the phosphate-buffered saline treatment group on either Day 5 or Day 15. Thus, clodronate liposomes can alleviate renal fibrosis and tissue damage and reduce the inflammatory cytokines IL-10 and TGF-β, suggesting that clodronate liposomes alleviate renal fibrosis may because of M1/M2 polarization.
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spelling doaj.art-d08922ea87694bbcb564d0265624ad242023-10-17T09:23:24ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2022.2149412Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transitionZhizhi Hu0Juan Zhan1Guangchang Pei2Rui Zeng3Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of ChinaDivision of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of ChinaDivision of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of ChinaDivision of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of ChinaAbstractClodronate liposomes are bisphosphonates encapsulated by liposomes that are known to induce macrophage depletion in vivo. In a previous study, clodronate liposomes improved renal ischemia/reperfusion (I/R) injury in mice, which may be due to effects on macrophage phenotypes. However, how inflammatory cytokines secretion participates is unknown. In this study, we investigated the effect of macrophages in the I/R kidney by depleting macrophages with clodronate liposomes and changing inflammatory cytokines. C57BL/6 mice underwent I/R injury with or without clodronate liposomes administration on Days 5 and 15. Tubular injury, collagen deposition, and fibrosis were detected and analyzed by histological staining, immunocytochemistry (IHC), flow cytometry (FACS), and reverse transcription–polymerase chain reaction (RT–PCR). Inflammatory cytokines were detected and analyzed by Western blotting and RT–PCR. We found that clodronate liposomes alleviated renal fibrosis and tissue damage on both Days 5 and 15. KIM-1, IL-10, and TGF-β were reduced significantly in the clodronate liposomes treatment group. However, TNF-α was not different between the clodronate liposomes treatment group and the phosphate-buffered saline treatment group on either Day 5 or Day 15. Thus, clodronate liposomes can alleviate renal fibrosis and tissue damage and reduce the inflammatory cytokines IL-10 and TGF-β, suggesting that clodronate liposomes alleviate renal fibrosis may because of M1/M2 polarization.https://www.tandfonline.com/doi/10.1080/0886022X.2022.2149412Ischemia/reperfusion injurymacrophagerenal fibrosisclodronate liposomes
spellingShingle Zhizhi Hu
Juan Zhan
Guangchang Pei
Rui Zeng
Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition
Renal Failure
Ischemia/reperfusion injury
macrophage
renal fibrosis
clodronate liposomes
title Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition
title_full Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition
title_fullStr Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition
title_full_unstemmed Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition
title_short Depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on AKI–CKD transition
title_sort depletion of macrophages with clodronate liposomes partially attenuates renal fibrosis on aki ckd transition
topic Ischemia/reperfusion injury
macrophage
renal fibrosis
clodronate liposomes
url https://www.tandfonline.com/doi/10.1080/0886022X.2022.2149412
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AT juanzhan depletionofmacrophageswithclodronateliposomespartiallyattenuatesrenalfibrosisonakickdtransition
AT guangchangpei depletionofmacrophageswithclodronateliposomespartiallyattenuatesrenalfibrosisonakickdtransition
AT ruizeng depletionofmacrophageswithclodronateliposomespartiallyattenuatesrenalfibrosisonakickdtransition