2026-10-12T09:27:12Z
https://api.figshare.com/v2/oai
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2026-10-01T12:00:39Z
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GABA ameliorates diabetic kidney disease-induced podocyte injury via JAML-FPR2 axis-mediated suppression of macrophage infiltration
Yibo Zhuang (9990782)
Chenlu Fu (25156413)
Zheng Guo (14989)
Yan Xu (14594)
Jun Zhou (6477)
Huiping Ni (25156416)
Aihua Zhang (174376)
Biochemistry
Microbiology
Cell Biology
Molecular Biology
Physiology
Pharmacology
Chemical Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Marine Biology
GABA
DKD
JAML
FPR2
M1 polarization
apoptosis
<p>This study demonstrates that gamma-aminobutyric acid (GABA) ameliorates diabetic kidney disease (DKD) by modulating macrophage-driven inflammation and podocyte injury through the JAML/FPR2 signaling axis. In streptozotocin (STZ)-induced DKD mice, GABA administration significantly improved renal function by reducing serum creatinine, urea nitrogen, 24-hour urine protein, attenuated glomerular hypertrophy/mesangial expansion, and suppressed pro-inflammatory cytokine production (TNF-α, IL-1β, iNOS) in renal tissue and serum. GABA inhibited glomerular macrophage infiltration (CD68<sup>+</sup> cells) and M1 polarization while mitigating renal apoptosis and podocyte injury by restoring nephrin and podocin. In a high glucose (HG)-stimulated macrophage-podocyte co-culture model, GABA reduced HG-induced podocyte apoptosis in a macrophage ratio-dependent manner by reversing M1 polarization and inflammatory cytokine overproduction. Mechanistically, GABA normalized DKD-elevated JAML expression in renal tissues and podocytes, while JAML overexpression abolished GABA’s renoprotective effects by reactivating inflammation, macrophage recruitment, and podocyte apoptosis. Co-IP confirmed JAML interacted with receptor formyl peptide receptor 2 (FPR2), which mediated DKD-driven macrophage infiltration, as FPR2 knockdown abrogated JAML-induced CD68<sup>+</sup> cell accumulation. Collectively, GABA alleviated DKD progression by disrupting the JAML/FPR2 axis to suppress macrophage-mediated inflammation and podocyte injury, highlighting its therapeutic potential for diabetic kidney disease.</p>
2026-10-01T12:00:39Z
Text
Journal contribution
10.6084/m9.figshare.34045524.v1
https://figshare.com/articles/journal_contribution/GABA_ameliorates_diabetic_kidney_disease-induced_podocyte_injury_via_JAML-FPR2_axis-mediated_suppression_of_macrophage_infiltration/34045524
CC BY 4.0