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.

Ying Zhu

Xinru Wang

Xiaoyun Zhou

Lexi Ding

Dan Liu

Huizhuo Xu

Biological Research

BIOLOGICAL RESEARCH 是一本开放获取、同行评审的期刊，涵盖实验生物学的不同领域，如生物化学、生物信息学、生物技术、细胞生物学、癌症、化学生物学、发育生物学、进化生物学、遗传学、基因组学、免疫学、海洋生物学、微生物学、分子生物学、神经科学、植物生物学、生理学、干细胞研究、结构生物学和系统生物学。

BIOLOGICAL RESEARCH is an open-access, peer-reviewed journal that covers various fields of experimental biology, including biochemistry, bioinformatics, biotechnology, cell biology, cancer research, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology, and systems biology.

BIOLOGICAL RESEARCH 是一本开放获取、同行评审的期刊，涵盖实验生物学的多个领域，包括生物化学、生物信息学、生物技术、细胞生物学、癌症研究、化学生物学、发育生物学、进化生物学、遗传学、基因组学、免疫学、海洋生物学、微生物学、分子生物学、神经科学、植物生物学、生理学、干细胞研究、结构生物学和系统生物学。

Biol Res

DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice

DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice, which may highlight novel insights into DR pathogenesis.

Category	Quartile
生物学	2
生物学, 生物学	2

DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice

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