HOXD9/APOC1 axis promotes macrophage M1 polarization to exacerbate diabetic kidney disease progression through activating NF-κB signaling pathway
Year: 2024
Type: article
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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Source: Hereditas
Authors: Ya Feng, Yalan Zhang, Fang Gao, Miaomiao Liu, Yangyan Luo
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W4404147733