DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice
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...
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Sociedad de Biología de Chile
2021
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oai:scielo:S0716-976020210001002212021-08-26DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy miceZhu,YingWang,XinruZhou,XiaoyunDing,LexiLiu,DanXu,Huizhuo DNMT1 PPARα DNA methylation Apoptosis Diabetic retinopathy 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.54 20212021-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100221en10.1186/s40659-021-00347-1 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
DNMT1 PPARα DNA methylation Apoptosis Diabetic retinopathy |
| spellingShingle |
DNMT1 PPARα DNA methylation Apoptosis Diabetic retinopathy Zhu,Ying Wang,Xinru Zhou,Xiaoyun Ding,Lexi Liu,Dan Xu,Huizhuo DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| description |
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. |
| author |
Zhu,Ying Wang,Xinru Zhou,Xiaoyun Ding,Lexi Liu,Dan Xu,Huizhuo |
| author_facet |
Zhu,Ying Wang,Xinru Zhou,Xiaoyun Ding,Lexi Liu,Dan Xu,Huizhuo |
| author_sort |
Zhu,Ying |
| title |
DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| title_short |
DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| title_full |
DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| title_fullStr |
DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| title_full_unstemmed |
DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| title_sort |
dnmt1-mediated pparα methylation aggravates damage of retinal tissues in diabetic retinopathy mice |
| publisher |
Sociedad de Biología de Chile |
| publishDate |
2021 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602021000100221 |
| work_keys_str_mv |
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| _version_ |
1718441618423414784 |