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| Status |
Public on Feb 17, 2026 |
| Title |
Splenic nerves NE-β2AR axis exacerbate septic acute kidney injury via modulating neutrophilic immunosuppression [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Sepsis is characterized by chronic inflammation and immunosuppression, two immune states that hinder effective infection control and significantly contribute to renal pathological damage. Recent studies have underscored the crucial role of splenic neuroimmune interactions in immune response regulation. However, the precise mechanisms and functions of splenic nerve regulation of splenic immune responses in sepsis-associated acute kidney injury (SA-AKI) remain obscure. Our research suggests that preemptive Splenic Denervation in mice can mitigate sepsis-induced renal injury, while local norepinephrine injection into the spleen exacerbates sepsis-induced kidney damage in the cecal ligation and puncture (CLP) mouse model. Targeted blockade of splenic β2-adrenergic receptor signaling leads to increased survival rates and diminished renal damage in the mice treated with CLP. Subsequent experiments involving local splenic administration of Gr-1 antibodies and myeloid cell-specific conditional knockout of Adrb2 in mice validate that during sepsis, NE/β2-AR signaling can impact splenic neutrophils, fostering the progression of acute sepsis. Mechanistic inquiries reveal that splenic Adrb2 signaling boosts neutrophil PGE2 signaling through the cAMP pathway, promoting Th1 activation, diminishing local bacterial infections, and ameliorating SA-AKI. Furthermore, Blocking ADRB2 or PGE2 synthesizing signal significantly modulates the immunosuppression effect of neutrophils, promoting anti-bacterial Th1 immune response. These studies elucidate the role of splenic NE-ADRB2 signaling in regulating neutrophil immunosuppressive functions, thereby influencing the advancement of sepsis and renal tissue damage.
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| Overall design |
Bone marrow cells were flushed from the tibia and femurs, neutrophils were sorted from bone marrow cells according to vendor instructions using a neutrophil isolation kit (130-097-658, Miltenyi Biotec). Single-cell suspensions were prepared using RPMI media. Cells were resuspended in MACS buffer and incubated with neutrophil biotin-antibody cocktail and anti-biotin micro-beads respectively. Neutrophils were negative selectively isolated by the magnetic cell separation method. The purity of the isolated neutrophils (>95%) was confirmed by flow cytometer. Neutrophils were prepared from bone of WT mice or Adrb2-/- mice as before. For in vitro experiments, neutrophils were stimulated with or without 20μM norepinephrine bitartrate (A2661, Sigma) for 1 hour, followed by stimulation with 100ng/mL LPS (L2880, Sigma-Aldrich) for 6 hours.
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| Citation missing |
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| BioProject |
PRJNA1224980 |
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| Submission date |
Feb 18, 2025 |
| Last update date |
Feb 17, 2026 |
| Contact name |
Xiaoqian Hu |
| E-mail(s) |
hux022325@gmail.com
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| Organization name |
Fudan University
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| Street address |
No. 130, Dongan Road, Xuhui District, Shanghai
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| City |
Shanghai |
| ZIP/Postal code |
200000 |
| Country |
China |
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| Platforms (1) |
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| Samples (12)
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| GSM8799942 |
WT mice,neutrophil+NE+LPS,rep1 |
| GSM8799943 |
WT mice,neutrophil+NE+LPS,rep2 |
| GSM8799944 |
WT mice,neutrophil+NE+LPS,rep3 |
| GSM8799945 |
ADRB2-KO mice,neutrophil+LPS,rep1 |
| GSM8799946 |
ADRB2-KO mice,neutrophil+LPS,rep2 |
| GSM8799947 |
ADRB2-KO mice,neutrophil+LPS,rep3 |
| GSM8799948 |
ADRB2-KO mice,neutrophil+NE+LPS,rep1 |
| GSM8799949 |
ADRB2-KO mice,neutrophil+NE+LPS,rep2 |
| GSM8799950 |
ADRB2-KO mice,neutrophil+NE+LPS,rep3 |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE289832_core_table_gene.txt.gz |
15.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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