ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Atorvastatin Inhibits the HIF1α-PPAR Axis, Which Is Essential for Maintaining the Function of Human Induced Pluripotent Stem Cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Effect of iPS cell culture medium on the differentiation potential of induced cardiac tissues.Scientific reports · 2025Article
- Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.Stem cell reports · 2025Review
- Sex hormone binding globulin (SHBG) modulates mitochondrial dynamics in PPARγ-depleted equine adipose derived stromal cells.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Role of hydroxymethylglutharyl-coenzyme A reductase in the induction of stem-like states in breast cancer.Journal of cancer research and clinical oncology · 2024Article
- Context-dependent regulation of lipid accumulation in adipocytes by a HIF1α-PPARγ feedback network.Cell systems · 2023Article
- Targeting the redox system for cardiovascular regeneration in aging.Aging cell · 2023Review
- Improved Production of Induced Pluripotent Stem Cells Using Dot Pattern Culture Plates.Tissue engineering. Part C, Methods · 2023Article
- Low colostrum intake results in potential accumulation of peroxisome lipid substrates in vaginal tissue of 3-week-old gilts.Biology open · 2023Article
- The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin.Current issues in molecular biology · 2023Article
- Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway.International journal of molecular sciences · 2023Article
- Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol-rRNA axis.BMC cancer · 2022Article
- Laminin-511 Activates the Human Induced Pluripotent Stem Cell Survival via α6β1 Integrin-Fyn-RhoA-ROCK Signaling.Stem cells and development · 2022Article
- Article
- Circulating stem cells and cardiovascular outcomes: from basic science to the clinic.European heart journal · 2020Review
- Chemokines and chemokine receptors: A new strategy for breast cancer therapy.Cancer medicine · 2020Review
- Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis.Journal of experimental & clinical cancer research : CR · 2020Article
- Oxygen-Glucose Deprivation/Reoxygenation-Induced Barrier Disruption at the Human Blood-Brain Barrier is Partially Mediated Through the HIF-1 Pathway.Neuromolecular medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We herein report a novel mechanism of action of statin preparations using a new drug discovery method. Milk fat globule-EGF factor 8 protein (MFG-E8) was identified from the secretory component of mouse embryonic fibroblast (MEF) as a cell adhesion-promoting factor effective for screening active cellular agents of human induced pluripotent stem cells (hiPSCs) in vitro using electrochemical impedance. Our analyses showed that atorvastatin did not cause death in myocardial cells differentiated from hiPSCs but reduced the pluripotent cell survival in vitro when using serum- and albumin-free media, and inhibited the ability to form teratomas in mice. This result could have been already the cytopathic effect of atorvastatin, and complete elimination of hiPSCs was confirmed in the xenotransplantation assay. The administration of atorvastatin to hiPSCs caused the expression of hypoxia inducible factor (HIF)1α mRNA to be unchanged at 6 hr and downregulated at 24 hr. In addition, the inhibition of the survival of hiPSCs was confirmed by HIF1α-peroxisome proliferator-activated receptor (PPAR) axis inhibition. These results suggest that the addition of atorvastatin to hiPSC cultures reduces the survival of pluripotent cells by suppressing the HIF1α-PPAR axis. In summary, the HIF1α-PPAR axis has an important role in maintaining the survival of pluripotent hiPSCs.
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