ArticlePloS one
Per2-Mediated Vascular Dysfunction Is Caused by the Upregulation of the Connective Tissue Growth Factor (CTGF).
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The trial behind it
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Circadian rhythm and the molecular clock in endothelial function of the cardiovascular system.Molecular and cellular biochemistry · 2026Review
- Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery.International journal of molecular sciences · 2024Review
- Circadian clock organization in the retina: From clock components to rod and cone pathways and visual function.Progress in retinal and eye research · 2023Review
- Neuronal Bmal1 regulates retinal angiogenesis and neovascularization in mice.Communications biology · 2022Article
- Association Between Pathophysiological Mechanisms of Diabetic Retinopathy and Parkinson's Disease.Cellular and molecular neurobiology · 2022Review
- A wrinkle in time: circadian biology in pulmonary vascular health and disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Circadian rhythms in diabetic retinopathy: an overview of pathogenesis and investigational drugs.Expert opinion on investigational drugs · 2020Review
- Eyeing the Extracellular Matrix in Vascular Development and Microvascular Diseases and Bridging the Divide between Vascular Mechanics and Function.International journal of molecular sciences · 2020Review
- The Retinal Circadian Clock and Photoreceptor Viability.Advances in experimental medicine and biology · 2018Review
- Conditional Deletion of Bmal1 Accentuates Microvascular and Macrovascular Injury.The American journal of pathology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Period 2-mutant mice (Per2m/m), which possess a circadian dysfunction, recapitulate the retinal vascular phenotype similar to diabetic retinopathy (DR). The vascular dysfunction in Per2m/m is associated with an increase in connective tissue growth factor (CTGF/CCN2). At the molecular level, CTGF gene expression is dependent on the canonical Wnt/β-catenin pathway. The nuclear binding of β-catenin to a transcription factor, lymphoid enhancer binding protein (Lef)/ T-cell factor (TCF/LEF), leads to downstream activation of CTGF. For this study, we hypothesized that the silencing of Per2 results in nuclear translocation and subsequent transactivation of the CTGF gene. To test this hypothesis, we performed immunofluorescence labeling for CTGF in retinal sections from wild-type (WT) and Per2m/m mice. Human retinal endothelial cells (HRECs) were transfected with siRNA for Per2, and the protein expression of CTGF and β-catenin was evaluated. The TCF/LEF luciferase reporter (TOPflash) assay was performed to validate the involvement of β-catenin in the activation of CTGF. Per2m/m retinas exhibited an increased CTGF immunostaining in ganglion cell layer and retinal endothelium. Silencing of Per2 using siRNA resulted in an upregulation of CTGF and β-catenin. The TOPflash assay revealed an increase in luminescence for HRECs transfected with Per2 siRNA. Our studies show that loss of Per2 results in an activation of CTGF via nuclear entry of β-catenin. Our study provides novel insight into the understanding of microvascular dysfunction in Per2m/m mice.
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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.