title: 4-Hydroxynonenal Regulates TNF-α Gene Transcription Indirectly via ETS1 and microRNA-29b in Human Adipocytes Induced From Adipose Tissue-Derived Stromal Cells.
abstract: Obesity is characterized by an accumulation of excessive body fat and can be diagnosed by a variety of measures, such as BMI. However, in some obese individuals, oxidative stress is also thought to be an important pathogenic mechanism of obesity-associated metabolic syndrome. Oxidative stress increases the lipid peroxidation product, 4-hydroxynonenal (4-HNE), which is one of the most abundant and active lipid peroxides. Within the adipose tissue, adipocytes are derived from adipose tissue-derived stromal cells (ADSCs), which play a key role in the generation and metabolism of adipose tissue. Additionally, obesity is associated with low-grade inflammation. Specific microRNAs (miRNAs) that regulate obesity-associated inflammation are largely dysregulated in metabolic syndrome (MS). In this study, we aim to confirm whether 4-HNE and miRNAs play a role in the regulation of TNF-α gene transcription. We enrolled six obese individuals who were referred to Harbin Medical University (Heilongjiang, China) and six nonobese control participants. Plasma 4-HNE levels of the 12 subjects were determined by ELISA. Using qRT-PCR, we measured ETS1, miR-29b, SP1, and TNF-α levels in subcutaneous white adipose tissue (WAT). Furthermore, we examined the relationship between ETS1 and TNF-α using a luciferase reporter assay and a ChIP assay. Our results suggest that ETS1 promotes TNF-α gene transcription in adipocytes. In addition, we demonstrated that 4-HNE promotes TNF-α gene transcription through the inhibition of the miR-29b → SP1 → TNF-α pathway and promotion of the ETS1 → TNF-α pathway. Anat Rec, 299:1145-1152, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, 150081, People's Republic of China.
authors.forename: Xi-Mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, 150081, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, 150081, People's Republic of China.
authors.forename: Qiu-Ming
authors.initials: QM
authors.lastname: Li
authors.affiliation: Teaching Experiment Center of Morphology, Harbin Medical University, Harbin, 150081, People's Republic of China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Chi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; C494041:ETS1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D014409:Tumor Necrosis Factor-alpha; C027576:4-hydroxy-2-nonenal
keywords: adipose stem cells; inflammation; miRNA; obesity; stromal cells