Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti-vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) increases the stability and activation of p53, which activates microRNA-34a (miRNA-34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA-34a that inhibits fibrosis. This study aimed to explore the role of the HIF-1α/p53/miRNA-34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia-induced HIF-1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE-19 cells (a human RPE cell line). HIF-1α-dependent p53 activation up-regulated miRNA-34a expression in ARPE-19 cells following hypoxia. Moreover, hypoxia-induced p53-dependent miRNA-34a inhibited the expression of Klotho in ARPE-19 cells. Additionally, the HIF-1α/p53/miRNA-34a/Klotho axis facilitated hypoxia-induced EMT in ARPE-19 cells. In vivo, blockade of the HIF-1α/p53/miRNA-34a/Klotho axis alleviated the formation of mouse laser-induced CNV and subretinal fibrosis. In short, the HIF-1α/p53/miRNA-34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.
Pubmed ID: 33438362
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Biotechnology company focused on developing robust gene delivery products, by using its proprietary technologies. Since 2004, we have worked with over 300 research labs in 20 different countries to provide gene delivery products and services using many viral platforms including recombinant adenoviruses, adeno-associated virus (AAV) and lentivirus.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsWelcome to the Neuroscience Information Framework Project, designed to serve the biomedical research community. NIF maintains the largest searchable collection of neuroscience data, the largest catalog of biomedical resources, and the largest ontology for neuroscience on the web. We welcome all feedback and suggestions and are actively looking for resource providers to make their resources accessible through NIF. Learn about the tools available to help you share your data and discover a dynamic inventory of Web-based neuroscience resources.
