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| Status |
Public on Dec 23, 2021 |
| Title |
Development of gene expression signatures for mice with renal ischemia repurfusion injury. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Acute kidney injury (AKI) is a global public health concern associated with high morbidity and mortality, and currently no therapeutic interventions reliably limit injury or speed recovery after AKI. Therefore, strategies to augment endogenous repair processes and retard associated profibrotic responses are urgently required. Among them, macrophages are attractive therapeutic targets for AKI because of their critical roles in tissue homeostasis and inflammation. Despite the differentiation of macrophages into morphologically and functionally distinct phenotypes M1/M2 and their clearance of dead cells (efferocytosis) have been increasingly linked to renal inflammation and repair in AKI, the underlying mechanisms of macrophage phenotype switching and efferocytosis during AKI are largely unclear. Here, we found that JAML (junctional adhesion molecule-like protein) deficiency protected against renal AKI. By generation of bone marrow chimeric mice and tubular-specific JAML conditional knockout mice, we demonstrated macrophage JAML primarily contributed to AKI. Mechanistically, JAML mediated macrophage phenotype polarization and efferocytosis, at least in part, through a C-type lectin receptor Mincle-dependent mechanism. In addition, we also found that JAML could induce endogenous Mincle ligand such as SAP130 release from dead or dying renal tubular epithelial cells and subsequent Mincle activation in macrophages, thereby also slightly contributing to AKI. Importantly, we observed a higher expression of JAML in the kidney from subjects with AKI and the level of JAML was correlated with serum creatinine. 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-Mincle mediated signaling pathways may provide a novel therapeutic strategy for patients with AKI.
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| Overall design |
The gene Jaml was knockd out in C57/6J background mice and was identified by western-blot and IHC,the results were showed in related articles. Three independent samples were performed for each group,after mice were anesthetized with an intraperitoneal injection of pentobarbital sodium (30 mg/kg body weight), a midline abdominal incision was made and bilateral renal pedicles were clipped for 40 minutes using microaneurysm clamps. At the end of the ischemic period, the vascular clamps were removed and the kidneys were observed for 5 minutes to ensure reflow process.
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| Contributor(s) |
Yi F |
| Citation(s) |
35616094, 35708906 |
| Submission date |
Dec 23, 2021 |
| Last update date |
Sep 14, 2022 |
| Contact name |
Wei Jinan Huang |
| E-mail(s) |
sy5409@sdu.edu.cn
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| Phone |
+86 18115191729
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| Organization name |
School of Basic Medical Sciences, Shandong University
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| Department |
Department of Pharmacology
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| Street address |
44# Wenhua Xi Road
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| City |
Jinan |
| ZIP/Postal code |
250012 |
| Country |
China |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA791894 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE192532_RAW.tar |
161.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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