ArticleCellular and molecular life sciences : CMLS2021
MiR-409-3p targets a MAP4K3-ZEB1-PLGF signaling axis and controls brown adipose tissue angiogenesis and insulin resistance.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Profiling miRNA changes in Epstein-Barr virus lytic infection identifies a function for BZLF1 in upregulating miRNAs from the DLK1-DIO3 locus.PLoS pathogens · 2025Article
- Organoids for Obesity-related Diseases: Disease Models and Drug Screening.Current stem cell research & therapy · 2025Review
- Placental growth factor mediates pathological uterine angiogenesis by activating the NFAT5-SGK1 signaling axis in the endometrium: implications for preeclampsia development.Biological research · 2024Article
- MicroRNA-409: Molecular functions and clinical applications in cancer.Biochemistry and biophysics reports · 2024Review
- MicroRNA-409-3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity.Nature reviews. Endocrinology · 2023Review
- Increasing serum miR-409-3p predicts the major adverse cardiac adverse events in elderly patients after hip fracture surgery.BMC musculoskeletal disorders · 2023Article
- OVOL2: an epithelial lineage determiner with emerging roles in energy homeostasis.Trends in cell biology · 2023Review
- Cardiac-to-adipose axis in metabolic homeostasis and diseases: special instructions from the heart.Cell & bioscience · 2023Review
- Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling.Molecular therapy. Nucleic acids · 2023Article
- Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice.Immunity & ageing : I & A · 2022Article
- Post-Transcriptional Effects of miRNAs on PCSK7 Expression and Function: miR-125a-5p, miR-143-3p, and miR-409-3p as Negative Regulators.Metabolites · 2022Article
- Article
- Identification and Validation of miR-222-3p and miR-409-3p as Plasma Biomarkers in Gestational Diabetes Mellitus Sharing Validated Target Genes Involved in Metabolic Homeostasis.International journal of molecular sciences · 2022Article
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Endothelial cells (ECs) within the microvasculature of brown adipose tissue (BAT) are important in regulating the plasticity of adipocytes in response to increased metabolic demand by modulating the angiogenic response. However, the mechanism of EC-adipocyte crosstalk during this process is not completely understood. We used RNA sequencing to profile microRNAs derived from BAT ECs of obese mice and identified an anti-angiogenic microRNA, miR-409-3p. MiR-409-3p overexpression inhibited EC angiogenic properties; whereas, its inhibition had the opposite effects. Mechanistic studies revealed that miR-409-3p targets ZEB1 and MAP4K3. Knockdown of ZEB1/MAP4K3 phenocopied the angiogenic effects of miR-409-3p. Adipocytes co-cultured with conditioned media from ECs deficient in miR-409-3p showed increased expression of BAT markers, UCP1 and CIDEA. We identified a pro-angiogenic growth factor, placental growth factor (PLGF), released from ECs in response to miR-409-3p inhibition. Deficiency of ZEB1 or MAP4K3 blocked the release of PLGF from ECs and PLGF stimulation of 3T3-L1 adipocytes increased UCP1 expression in a miR-409-3p dependent manner. MiR-409-3p neutralization improved BAT angiogenesis, glucose and insulin tolerance, and energy expenditure in mice with diet-induced obesity. These findings establish miR-409-3p as a critical regulator of EC-BAT crosstalk by modulating a ZEB1-MAP4K3-PLGF signaling axis, providing new insights for therapeutic intervention in obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.