Back to Search
Start Over
High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression
- Source :
- Journal of Diabetes Research, Vol 2020 (2020), Journal of Diabetes Research
- Publication Year :
- 2020
- Publisher :
- Hindawi Limited, 2020.
-
Abstract
- Cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) overexpression results in endothelial apoptosis, thus mediating vascular endothelial injury in hyperglycaemia. E26 transformation-specific sequence transcription factor-1 (ESE-1), which belongs to the E26 transformation-specific family of transcription factors, has been demonstrated to be involved in COX2 and iNOS gene transcription. Our previous study indicated that SET domain-containing protein 8 (SETD8) downregulation is involved in high glucose-mediated endothelial inflammation in human umbilical vein endothelial cells (HUVECs). Here, we report that SETD8 plays a major role in hyperglycaemia-induced COX2 and iNOS expression. In HUVECs, upregulation of ESE-1 expression was related to high glucose-mediated apoptosis and COX2 and iNOS expression. High glucose inhibited SETD8 expression, and overexpression of SETD8 diminished the effects of high glucose treatment. Consistently, RNA silencing of SETD8 led to the opposite effect. Furthermore, SETD8 was found to interact with specificity protein 1 (SP1). Blockade of SP1 protected against high glucose-mediated endothelial injury. Mechanistically, we showed that H4K20me1, a downstream target of SETD8, and SP1 were enriched at the ESE-1 promoter region by ChIP assay. Luciferase reporter assays indicated that SETD8 overexpression attenuated ESE-1 promoter activity and augmented the inhibitory effect of siSP1 on ESE-1 promoter activity. In general, our data indicate that SETD8 interacts with SP1 to coregulate ESE-1 expression, which is involved in hyperglycaemia-mediated endothelial apoptosis in HUVECs.
- Subjects :
- 0301 basic medicine
Article Subject
Endocrinology, Diabetes and Metabolism
Down-Regulation
Nitric Oxide Synthase Type II
Apoptosis
Diseases of the endocrine glands. Clinical endocrinology
Umbilical vein
03 medical and health sciences
0302 clinical medicine
Endocrinology
Downregulation and upregulation
Transcription (biology)
Human Umbilical Vein Endothelial Cells
Humans
Transcription factor
biology
Chemistry
Promoter
Histone-Lysine N-Methyltransferase
RC648-665
Up-Regulation
Cell biology
Nitric oxide synthase
RNA silencing
Glucose
030104 developmental biology
Cyclooxygenase 2
030220 oncology & carcinogenesis
biology.protein
Research Article
Subjects
Details
- ISSN :
- 23146753 and 23146745
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Journal of Diabetes Research
- Accession number :
- edsair.doi.dedup.....35469633c1f13cbc2dfc9339fdecbd92