RETRACTED: KLF4/Ch25h axis activated by metformin suppresses EndoMT in human umbilical vein endothelial cells
Autor: | Zhao Li, Beixin Yu, Yingying Wu |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Kruppel-Like Transcription Factors Biophysics Biochemistry Umbilical vein Epigenesis Genetic Mesoderm Kruppel-Like Factor 4 03 medical and health sciences 0302 clinical medicine Internal medicine Human Umbilical Vein Endothelial Cells medicine Animals Humans Endothelium Endothelial dysfunction Liver X receptor Molecular Biology Liver X Receptors Chemistry Mesenchymal stem cell Cell Biology medicine.disease Metformin Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology KLF4 030220 oncology & carcinogenesis Steroid Hydroxylases DNA methylation Platelet factor 4 Signal Transduction medicine.drug |
Zdroj: | Biochemical and Biophysical Research Communications. 522:838-844 |
ISSN: | 0006-291X |
Popis: | Metformin, an anti-hyperglycemia drug, protected endothelial cells (ECs) from dysfunction while high glucose (HG) caused endothelial dysfunction. Previously, we found that metformin suppressed endothelial-to-mesenchymal transition (EndoMT), a cellular process that promoted endothelial dysfunction. However, the involved mechanism is still unclear. In this study, we found that metformin increased the expression of kruppel-like factor 4 (KLF4) and cholesterol-25-hydroxylase (Ch25h) while HG decreased the expression of KLF4 and Ch25h. In addition, HG promoted EndoMT indicting by the decrease of endothelial maker genes and increase of mesenchymal maker genes. Furthermore, RNA sequence (RNA-seq) data showed that KLF4 suppressed EndoMT. Moreover, we proved that metformin increased Ch25h expression through not only KLF4 but also epigenetic modification including DNA methylation and active histone modification. Lastly, we proved that Ch25h/25 hydroxycholesterol (25 HC)/Liver X receptor α (LXRα) suppressed EndoMT. Altogether, our study demonstrated that KLF4/Ch25h/axis activated by metformin suppressed EndoMT. Therefore, KLF4/Ch25h/axis may be a new potential therapeutic target for endothelial dysfunction diseases. |
Databáze: | OpenAIRE |
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