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ResearchIn-Press PreviewNephrology Open Access | 10.1172/jci.insight.158571

JAML promotes acute kidney injury mainly through a macrophage-dependent mechanism

Wei Huang,1 Bi-Ou Wang,1 Yunfeng Hou,2 Yi Fu,1 Sijia Cui,3 Jinghan Zhu,1 Xinyu Zhan,1 Rongkun Li,1 Wei Tang,1 Jichao Wu,1 Ziying Wang,1 Mei Wang,1 Xiaojie Wang,1 Yan Zhang,1 Min Liu,1 Yusheng Xie,1 Yu Sun,1 and Fan Yi1

1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

Find articles by Huang, W. in: JCI | PubMed | Google Scholar

1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

Find articles by Wang, B. in: JCI | PubMed | Google Scholar

1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

Find articles by Cui, S. in: JCI | PubMed | Google Scholar

1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

Find articles by Zhu, J. in: JCI | PubMed | Google Scholar

1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China

2Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Affiliated Hospital of Shandong First Medical University, Jinan, China

3Department of Pharmacology, School of Basic Medical Sciences, Shandong University., Jinan, China

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Published June 16, 2022 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.158571.
Copyright © 2022, Huang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 16, 2022 - Version history
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Abstract

Although macrophages are undoubtedly attractive therapeutic targets for acute kidney injury (AKI) because of their critical roles in renal inflammation and repair, the underlying mechanisms of macrophage phenotype switching and efferocytosis in the regulation of inflammatory responses during AKI are still largely unclear. The present study was to elucidate the role of JAML (junctional adhesion molecule-like protein) in the pathogenesis of AKI. We found that JAML was significantly up-regulated in the kidney from two different murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI. By generation of bone marrow chimeric mice, macrophage-specific and tubular-specific Jaml conditional knockout mice, we demonstrated JAML promotes AKI mainly via a macrophage-dependent mechanism and found that JAML-mediated macrophage phenotype polarization and efferocytosis is one of critical signal transduction pathways linking inflammatory responses to AKI. Mechanistically, the effects of JAML on the regulation of macrophages was at least in part, associated with a Mincle-dependent mechanism. Collectively, our studies for the first time explore new biological functions of JAML in macrophages and conclude that JAML is an important mediator and biomarker of AKI. Pharmacologic targeting of JAML mediated signaling pathways at multiple levels may provide a novel therapeutic strategy for patients with AKI.

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