DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice
Biol. Res
; 54: 25-25, 2021. ilus, graf
Article
in English
| LILACS
| ID: biblio-1505814
Responsible library:
CL1.1
ABSTRACT
BACKGROUND:
Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR.METHODS:
Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model. DR mouse model was established by streptozotocin injection, and then received 5-Aza-2-deoxycytidine (DAC; DNA methyltransferase inhibitor) treatment. Hematoxylin-eosin staining was performed to assess retinal tissue damage. PPARα methylation was examined by Methylation-Specific PCR. Flow cytometry and DCFH-DA fluorescent probe was used to estimate apoptosis and reactive oxygen species (ROS). The interaction between DNA methyltransferase-1 (DNMT1) and PPARα promoter was examined by Chromatin Immunoprecipitation. Quantitative real-time PCR and western blot were performed to assess gene and protein expression.RESULTS:
HG treatment enhanced the methylation levels of PPARα, and repressed PPARα expression in HRCPs. The levels of apoptotic cells and ROS were significantly increased in HRCPs in the presence of HG. Moreover, DNMT1 was highly expressed in HG-treated HRCPs, and DNMT1 interacted with PPARα promoter. PPARα overexpression suppressed apoptosis and ROS levels of HRCPs, which was rescued by DNMT1 up-regulation. In DR mice, DAC treatment inhibited PPARα methylation and reduced damage of retinal tissues.CONCLUSION:
DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice. Thus, this study may highlight novel insights into DR pathogenesis.
Full text:
Available
Collection:
International databases
Health context:
SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases
Health problem:
Cardiovascular Disease
/
Diabetes Mellitus
/
Endocrine System Diseases
Database:
LILACS
Main subject:
Retina
/
PPAR alpha
/
Diabetic Retinopathy
/
DNA (Cytosine-5-)-Methyltransferase 1
Limits:
Animals
/
Humans
Language:
English
Journal:
Biol. Res
Journal subject:
Biology
Year:
2021
Document type:
Article
Affiliation country:
China
Institution/Affiliation country:
Central South University/CN
/
The First Hospital of Changsha/CN