Related Experiment Video
Updated: Mar 1, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
ox-LDL increases microRNA-29a transcription through upregulating YY1 and STAT1 in macrophages
Dongdong Jian1, Bing Dai1, Xiaotong Hu2
1Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, P.R. China.
Abstract:
Macrophages and oxidized low-density lipoprotein (ox-LDL) have been verified playing vital roles in the pathogenesis of atherosclerosis (AS). Previous studies demonstrated that microRNA-29a (miR-29a) was upregulated in many atherogenic process and cells, thus acting as an important participant in AS. But the detailed regulation mechanism of miR-29a in AS has not been fully understood. In our study, we demonstrated a positive feedback loop of ox-LDL-SRA-miR-29a. Furthermore, we found that YY1 and STAT1 were upregulated in ox-LDL-stimulating macrophages followed by translocation in the nucleus and binding to the transcriptional promoter region of miR-29a, thus leading to the increase of miR-29a expression. In addition, we demonstrated that JAK1/2 signaling was involved in miR-29a upregulation. Finally, we found that miR-29a played important roles in the secretion of proinflammation factors and lipid uptake in macrophages. We uncovered the molecular mechanism and provide novel insights into the function and regulatory network of miR-29a expression regulated by ox-LDL in macrophages.
Insights
Oxidized LDL triggers a feedback loop increasing microRNA-29a in macrophages, promoting atherosclerosis. This involves transcription factors YY1, STAT1, and JAK1/2 signaling, impacting inflammation and lipid uptake.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- Macrophages and oxidized low-density lipoprotein (ox-LDL) are key in atherosclerosis (AS) pathogenesis.
- MicroRNA-29a (miR-29a) is upregulated in atherogenic processes, but its regulation in AS is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism regulating miR-29a expression by ox-LDL in macrophages.
- To investigate the role of miR-29a in macrophage function during AS.
Main Methods:
- Investigated the ox-LDL-SRA-miR-29a feedback loop.
- Assessed the role of transcription factors YY1 and STAT1 in miR-29a promoter activity.
- Examined the involvement of JAK1/2 signaling pathway.
- Evaluated miR-29a's impact on pro-inflammatory cytokine secretion and lipid uptake in macrophages.
Main Results:
- A positive feedback loop involving ox-LDL, SRA, and miR-29a was identified.
- Ox-LDL upregulated YY1 and STAT1, which bind to the miR-29a promoter, increasing its expression.
- JAK1/2 signaling pathway was implicated in ox-LDL-induced miR-29a upregulation.
- miR-29a significantly influenced pro-inflammation factor secretion and lipid uptake in macrophages.
Conclusions:
- Uncovered a novel molecular mechanism for ox-LDL-mediated miR-29a regulation in macrophages.
- Provided new insights into the function and regulatory network of miR-29a in atherosclerosis.
- Identified a potential therapeutic target for AS treatment.
Related Concept Videos
01:38Inflammation
02:23Master Transcription Regulators
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...