Serum-deprivation response of ARPE-19 cells; expression patterns relevant to age-related macular degeneration.

Autor: Peterson KM; Molecular Structure and Functional Genomics Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America., Mishra S; Molecular Structure and Functional Genomics Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America., Asaki E; Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America., Powell JI; Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America., He Y; Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America., Berger AE; Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America., Rajapakse D; Molecular Structure and Functional Genomics Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America., Wistow G; Molecular Structure and Functional Genomics Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Sep 26; Vol. 19 (9), pp. e0293383. Date of Electronic Publication: 2024 Sep 26 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0293383
Abstrakt: ARPE-19 cells are derived from adult human retinal pigment epithelium (RPE). The response of these cells to the stress of serum deprivation mimics some important processes relevant to age-related macular degeneration (AMD). Here we extend the characterization of this response using RNASeq and EGSEA gene set analysis of ARPE-19 cells over nine days of serum deprivation. This experiment confirmed the up-regulation of cholesterol and lipid-associated pathways that increase cholesterol levels in these cells. The gene expression analysis also identified other pathways relevant to AMD progression. There were significant changes in extracellular matrix gene expression, notably a switch from expression of collagen IV, a key component of Bruch's membrane (part of the blood-retina barrier), to expression of a fibrosis-like collagen type I matrix. Changes in the expression profile of the extracellular matrix led to the discovery that amelotin is induced in AMD and is associated with the development of the calcium deposits seen in late-stage geographic atrophy. The transcriptional profiles of other pathways, including inflammation, complement, and coagulation, were also modified, consistent with immune response patterns seen in AMD. As previously noted, the cells resist apoptosis and autophagy but instead initiate a gene expression pattern characteristic of senescence, consistent with the maintenance of barrier function even as other aspects of RPE function are compromised. Other differentially regulated genes were identified that open new avenues for investigation. Our results suggest that ARPE-19 cells maintain significant stress responses characteristic of native RPE that are informative for AMD. As such, they provide a convenient system for discovery and for testing potential therapeutic interventions.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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