ArticleBiochimica et biophysica acta. Molecular basis of disease2017
Role of PARP-1 as a novel transcriptional regulator of MMP-9 in diabetic retinopathy.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- Diabetic retinopathy: shaped by the "hidden hand" of post-translational modifications.Molecular neurodegeneration · 2026Review
- Key role of transcription factors network in proliferative vitreoretinal diseases development.Cell & bioscience · 2026Review
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Protective role of zingerone against high glucose-Induced retinal pigment epithelial cell damage through modulation of the TRPM2 channel pathway.Molecular biology reports · 2026Article
- The Role of ADAM9 and MMP9 in Diabetic Retinopathy: Insights from Ocular Parameters.International journal of molecular sciences · 2025Article
- Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.Pharmaceutics · 2025Review
- Research Hotspots and Trends of RNA Research in Diabetic Retinopathy: Insights From Bibliometric Analysis.Endocrine, metabolic & immune disorders drug targets · 2025Review
- From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Factors influencing glycocalyx degradation: a narrative review.Frontiers in immunology · 2024Review
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- Dysregulation of histone deacetylases in ocular diseases.Archives of pharmacal research · 2024Review
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
- Cross Talks between Oxidative Stress, Inflammation and Epigenetics in Diabetic Retinopathy.Cells · 2023Review
- Impaired mitochondrial dynamics and removal of the damaged mitochondria in diabetic retinopathy.Frontiers in endocrinology · 2023Article
- Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Combined analysis of whole-exome sequencing and RNA sequencing in type 2 diabetes mellitus patients with thirst and fatigue.Diabetology & metabolic syndrome · 2022Article
- Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina.Human molecular genetics · 2022Article
- Therapeutic Potentials of Poly (ADP-Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Intermittent Fasting to the Eye: A New Dimension Involved in Physiological and Pathological Changes.Frontiers in medicine · 2022Review
- PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination.Cell reports · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In diabetes, matrix metalloproteinase-9 (MMP-9) is activated, which damages mitochondria, resulting in accelerated capillary cell apoptosis. Regulation of MMP-9 is controlled by multiple transcription factors including nuclear factor-kB (NF-kB) and activator protein-1 (AP-1). Binding of these transcription factors, however, can be regulated by poly(ADP-ribose) polymerase-1 (PARP-1), which forms a strong initiation complex at the promoter region and facilitates multiple rounds of gene transcription. This complex formation with the transcription factors is regulated by posttranslational acetylation of PARP-1, and in diabetes, the deacetylating enzyme, Sirt1, is inhibited. Our aim was to understand the role of PARP-1 in transcriptional regulation of MMP-9 in the development of diabetic retinopathy. Using human retinal endothelial cells, the effect of PARP-1 inhibition (pharmacologically by PJ34, 1μM; or genetically by its siRNA) on MMP-9 expression was investigated. The effect of PARP-1 acetylation on its binding at the MMP-9 promoter, and with NF-kB/AP-1, was investigated in the cells transfected with Sirt1. In vitro results were validated in the retinal microvessels from diabetic mice either administered PJ34, or overexpressing Sirt1. Inhibition of PARP-1 ameliorated hyperglycemia-induced increase in the binding of NF-kB/AP-1 at the MMP-9 promoter, decreased MMP-9 expression and ameliorated mitochondrial damage. Overexpression of Sirt1 attenuated diabetes-induced increase in PARP-1 binding at MMP-9 promoter or with NF-kB/AP-1. Thus, PARP-1, via manipulating the binding of NF-kB/AP-1 at the MMP-9 promoter, regulates MMP-9 expression, which helps maintain mitochondrial homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.