Upregulation of miR-210–5p impairs dead cell clearance by macrophages through the inhibition of Sp1-and HSCARG-dependent NADPH oxidase pathway
| Autor: | Tsong-Long Hwang, Hsi-Lung Hsieh, Chang-Fu Kuo, Yi-Hsuan Wu, Ao-Ho Hsieh, Yen-Fan Chan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Sp1 Transcription Factor Protein degradation Biochemistry Peripheral blood mononuclear cell 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Physiology (medical) Humans Lupus Erythematosus Systemic Dead cell chemistry.chemical_classification Gene knockdown Reactive oxygen species NADPH oxidase biology Chemistry Superoxide Macrophages NADPH Oxidases Up-Regulation Cell biology MicroRNAs 030104 developmental biology Leukocytes Mononuclear biology.protein Oxidoreductases 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Free Radical Biology and Medicine. 172:441-450 |
| ISSN: | 0891-5849 |
| Popis: | The deficiency of dead cell clearance is a prominent pathogenic factor in systemic lupus erythematosus (SLE). In this study, the overexpression of miR-210-5p resulted in the accumulation of secondary necrotic cells (SNECs) in macrophages through the reduction of protein degradation. The upreguation of miR-210-5p inhibited NADPH oxidase (NOX) activation, reactive oxygen species (ROS) generation, and SNEC clearance. miR-210-5p overexpression suppressed Sp1 and HSCARG expression, and the knockdown of SP1 and HSCARG inhibited NOX expression and superoxide production in macrophages. Furthermore, patients with active SLE expressed a higher level of miR-210-5p and lower expression of SP1 and HSCARG in peripheral blood mononuclear cells. In summary, our findings indicate that the upregulation of miR-210-5p increases the accumulation of SNECs through a decrease in the Sp1-and HSCARG-mediated NOX activity and ROS generation in macrophages. Our results also suggest that targeting miR-210-5p may have therapeutic potential for SLE. |
| Databáze: | OpenAIRE |
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