Experimental cell research · 2026
ZFP36 and CEBPA are macrophage-associated prognostic biomarkers linked to glomerular endothelial inflammation in ANCA-associated glomerulonephritis.
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Ni Anqi, Zhu Xinqi, Wang Junni, Chen Liangliang, Zhu Huanhuan, Miao Jin, Xu Jianhang, Ren Pingping, Chen Jianghua, Xiao Liang, Han Fei
Аннотация
BACKGROUND: Macrophages are critical in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). This study investigated macrophage-associated genes (MAGs) ZFP36 and CEBPA in AAGN renal tissue and evaluated their role in glomerular endothelial injury.
METHODS: Macrophage infiltration and its association with prognosis were assessed in renal tissues via immunohistochemistry. ZFP36 and CEBPA were identified via the Gene Expression Omnibus (GEO) database. Their expression in AAGN and correlation with immune cell infiltration and clinical indicators were analyzed. Serum from healthy individuals and AAGN patients was used to stimulate human renal glomerular endothelial cells (HRGECs), and ZFP36 and CEBPA expression was measured using western blotting and real-time PCR. Functional studies included gene knockdown and overexpression, actinomycin D chase assays, NF-κB inhibition, and a direct co-culture system with THP-1-derived macrophages.
RESULTS: AAGN renal tissues showed marked immune infiltration and macrophage activation, predicting poor prognosis. ZFP36 was downregulated and low ZFP36 expression correlated with poor prognosis, while CEBPA was upregulated and high CEBPA expression correlated with poor prognosis. Immunofluorescence demonstrated partial localization of both proteins in CD31-positive glomerular endothelial areas. In HRGECs, ZFP36 attenuated inflammatory responses, accelerated TNF-α and IL6 mRNA decay, and was associated with reduced NF-κB activation, whereas CEBPA promoted endothelial inflammatory mediator expression. In co-culture experiments, endothelial ZFP36 reduced, whereas endothelial CEBPA increased, TNF-α production in adjacent macrophages.
CONCLUSIONS: ZFP36 and CEBPA are macrophage-associated genes linked to immune infiltration, renal prognosis, and endothelial inflammatory responses in AAGN, and may serve as potential tissue biomarkers and therapeutic targets.
METHODS: Macrophage infiltration and its association with prognosis were assessed in renal tissues via immunohistochemistry. ZFP36 and CEBPA were identified via the Gene Expression Omnibus (GEO) database. Their expression in AAGN and correlation with immune cell infiltration and clinical indicators were analyzed. Serum from healthy individuals and AAGN patients was used to stimulate human renal glomerular endothelial cells (HRGECs), and ZFP36 and CEBPA expression was measured using western blotting and real-time PCR. Functional studies included gene knockdown and overexpression, actinomycin D chase assays, NF-κB inhibition, and a direct co-culture system with THP-1-derived macrophages.
RESULTS: AAGN renal tissues showed marked immune infiltration and macrophage activation, predicting poor prognosis. ZFP36 was downregulated and low ZFP36 expression correlated with poor prognosis, while CEBPA was upregulated and high CEBPA expression correlated with poor prognosis. Immunofluorescence demonstrated partial localization of both proteins in CD31-positive glomerular endothelial areas. In HRGECs, ZFP36 attenuated inflammatory responses, accelerated TNF-α and IL6 mRNA decay, and was associated with reduced NF-κB activation, whereas CEBPA promoted endothelial inflammatory mediator expression. In co-culture experiments, endothelial ZFP36 reduced, whereas endothelial CEBPA increased, TNF-α production in adjacent macrophages.
CONCLUSIONS: ZFP36 and CEBPA are macrophage-associated genes linked to immune infiltration, renal prognosis, and endothelial inflammatory responses in AAGN, and may serve as potential tissue biomarkers and therapeutic targets.