HOXD9/APOC1 axis promotes macrophage M1 polarization to exacerbate diabetic kidney disease progression through activating NF-κB signaling pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39511608", "kind": "science-record", "revision": 4, "content_hash": "sha256:77bb9b63a86b3cd5ceedd40631a4297228cd52f952a9e73e3de45c0663b04bf3", "created_at": "2026-11-01T20:29:46Z", "updated_at": "2026-11-01T22:55:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "HOXD9/APOC1 axis promotes macrophage M1 polarization to exacerbate diabetic kidney disease progression through activating NF-κB signaling pathway.", "doi": "10.1186/s41065-024-00345-9", "pmid": "39511608", "authors": ["Ya Feng", "Yalan Zhang", "Fang Gao", "Miaomiao Liu", "Yangyan Luo"], "journal": "Hereditas", "year": 2024, "abstract": "BACKGROUND: Diabetic kidney disease (DKD) is a complication caused by end-stage diabetes mellitus and usually results in glomerular podocyte injury. Exosomes are important for intercellular information exchange. However, the effect of podocyte exosomes on DKD has not been elucidated.\nMETHODS: GEO, PROMO, and GSE1009 databases were used to identify the gene APOC1 and transcription factor HOXD9. qRT-PCR, western blot, and transmission electron microscopy (TEM) were investigated to confirm APOC1 change in high glucose-treated podocytes and exosomes. Flow cytometry, immunofluorescence, qPCR, immunoblotting, wound healing, Transwell invasion assays, dual luciferase assay, and ChIP-PCR assay were performed to detect the effect of APOC1 and HOXD9 on macrophage polarization in high glucose-treated podocytes and exosomes. qRT-PCR and immunoblotting assays were employed to assess the impact of APOC1 knockdown on the M1 polarization of macrophages in response to liraglutide treatment.\nRESULTS: The results suggested that the expression of APOC1 in human podocytes (HPC) and exosomes was elevated. High glucose-treated HPC exosomes promoted macrophage M1-type polarization, which was reversed by adding sh-APOC1. Afterward, HOXD9 was identified as a potential transcription factor for APOC1. Knockdown of HOXD9 led to macrophage M2 polarization, and overexpression of APOC1 polarized macrophage M1. In addition, enhanced p65 phosphorylation verified that HOXD9/APOC1 induced macrophage M1-type polarization by activating the NF-κB signaling pathway. Knocking down APOC1 enhanced the inhibitory effect of liraglutide on macrophage M1 polarization.\nCONCLUSION: Our findings highlighted that HOXD9/APOC1 was a key player in causing podocyte injury in diabetic kidney disease and led to macrophage M1 polarization through the NF-κB signaling pathway.", "claims": [{"id": "claim-method", "statement": "The experiment was repeated at least three times and the data were expressed as mean ± standard deviation, and unpaired Student’s t-test was used to analyze the differences between the two groups. Differences between multiple groups were analyzed using one-way ANOVA with Tukey’s post-hoc test. p < 0.05 (two-tailed) was considered statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39511608", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "The experiment was repeated at least three times and the data were expressed as mean ± standard deviation, and unpaired Student’s t-test was used to analyze the differences between the two groups. 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