ArticlePloS one2015
αvβ5 Integrin/FAK/PGC-1α Pathway Confers Protective Effects on Retinal Pigment Epithelium.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Retinal Pigment Epithelium Phagocytosis and Retinal Degenerative Diseases.Aging and disease · 2025Pooled it
- The roles of glycerophospholipids in the aging retina and age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Retinitis Pigmentosa-Associated Gene TRIM49 Regulates ULK1-Mediated Autophagy and Photoreceptor Phagocytosis by the Retinal Pigment Epithelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PNPLA6 regulates retinal homeostasis by choline through phospholipid turnover.Nature communications · 2025Article
- Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage.Experimental and molecular pathology · 2023Article
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1Alpha (PGC-1α): A Transcriptional Regulator at the Interface of Aging and Age-Related Macular Degeneration?Advances in experimental medicine and biology · 2023Article
- Review
- FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress.Scientific reports · 2021Article
- Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration.Progress in retinal and eye research · 2020Review
- Axonal debris accumulates in corneal epithelial cells after intraepithelial corneal nerves are damaged: A focused Ion Beam Scanning Electron Microscopy (FIB-SEM) study.Experimental eye research · 2020Article
- Senescence in the pathogenesis of age-related macular degeneration.Cellular and molecular life sciences : CMLS · 2020Review
- Fucoidan Suppresses Mitochondrial Dysfunction and Cell Death against 1-Methyl-4-Phenylpyridinum-Induced Neuronal Cytotoxicity via Regulation of PGC-1α Expression.Marine drugs · 2019Article
- Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration.Life science alliance · 2019Article
- Article
- Genomic/proteomic analyses of dexamethasone-treated human trabecular meshwork cells reveal a role for GULP1 and ABR in phagocytosis.Molecular vision · 2019Article
- PGC-1α Protects RPE Cells of the Aging Retina against Oxidative Stress-Induced Degeneration through the Regulation of Senescence and Mitochondrial Quality Control. The Significance for AMD Pathogenesis.International journal of molecular sciences · 2018Review
- Differential Phagocytic Properties of CD45Frontiers in immunology · 2018Article
- Pharmaceutical Induction of PGC-1Oxidative medicine and cellular longevity · 2018Article
- Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?Oxidative medicine and cellular longevity · 2017Review
- Integrin-FAK signaling rapidly and potently promotes mitochondrial function through STAT3.Cell communication and signaling : CCS · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo elucidate the mechanism of the induction of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by photoreceptor outer segments (POS) and its effects on retinal pigment epithelium (RPE).
methodsPGC-1α upregulation by POS was confirmed in ARPE-19 cells and in RPE ex vivo. To elucidate the mechanism, siRNAs against β5 integrin, CD36, Mer tyrosine kinase (MerTK), and Atg5, blocking antibodies against CD36 and MerTK, and a specific inhibitor for focal adhesion kinase (FAK) were used. We examined the effect of POS-induced PGC-1α upregulation on the levels of reactive oxygen species (ROS), mitochondrial biogenesis, senescence-associated β-galactosidase (SA-β-gal) after H2O2 treatment, and lysosomal activity. Lysosomal activity was evaluated through transcriptional factor EB and its target genes, and the activity of cathepsin D. Lipid metabolism after POS treatment was assessed using Oil Red O and BODIPY C11. RPE phenotypes of PGC-1α-deficient mice were examined.
resultsPOS-induced PGC-1α upregulation was suppressed by siRNA against β5 integrin and a FAK inhibitor. siRNAs and blocking antibodies against CD36 and MerTK enhanced the effect of POS on PGC-1α. The upregulation of PGC-1α increased the levels of mRNA for antioxidant enzymes and stimulated mitochondrial biogenesis, decreased ROS levels, and reduced SA-β-gal staining in H2O2-treated ARPE-19 cells. PGC-1α was critical for lysosomal activity and lipid metabolism after POS treatment. PGC-1α-deficient mice demonstrated an accumulation of type 2 lysosomes in RPE, thickening of Bruch's membrane, and poor choriocapillaris vasculature.
conclusionsThe binding, but not the internalization of POS confers protective effects on RPE cells through the αvβ5 integrin/FAK/PGC-1α pathway.
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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.