Effects of Inflammatory Factor Expression Regulated by 12/15 Lipoxygenase on Obesity-Related Nephropathy.
Nutrients
; 14(13)2022 Jun 30.
Article
em En
| MEDLINE
| ID: mdl-35807921
ABSTRACT
BACKGROUND:
It has been demonstrated that 12/15-lipoxygenase (LO) contributes to insulin resistance by promoting beta cells' exposure to inflammation. We investigate the mechanism by which 12/15-LO regulates the expression of inflammatory factors in obesity-related glomerular disease (ORG).METHODS:
Glomerular mesangial cells were treated with metabolite of 12/15-LO, and the expression of inflammatory factors was measured. Cell histones methylation in 12/15-LO related metabolic memory process were evaluated by chromatin immunoprecipitation (ChIP) assays. Wild-type (WT) and 12/15-LO knockout mice were fed a high-fat diet (HFD) to induce ORG.RESULTS:
12(S)-HETE increased TNF-α, MCP-1, and IL-6 mRNA expression. Inhibition of 12/15-LO reduced the expression of inflammatory factors stimulated by PA or TNF-α. ChIP assays showed that 12(S)-HETE increased H3K4me modification in the TNF-α, IL-6, and MCP-1 gene promoters, and decreased H3K9me3 modification in the MCP-1 and IL-6 gene promoter. Urinary albumin excretion was greater in HFD-fed than in standard fat diet-fed mice, but both urinary protein and microalbumin amounts were lower in HFD-fed 12/15-LO knockout than in WT mice. The levels of TNF-α, IL-6, and MCP-1 in serum and renal cortex were higher in WT than in 12/15-LO knockout mice.CONCLUSIONS:
12/15-LO may regulate the expression of inflammatory factors in ORG by methylation of histones in the promoter regions of genes encoding inflammatory factors, sustaining the inflammatory phenotype of ORG.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Araquidonato 15-Lipoxigenase
/
Histonas
Limite:
Animals
Idioma:
En
Revista:
Nutrients
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China