ArticleThe Journal of biological chemistry2015
HTRA1 (high temperature requirement A serine peptidase 1) gene is transcriptionally regulated by insertion/deletion nucleotides located at the 3' end of the ARMS2 (age-related maculopathy susceptibility 2) gene in patients with age-related macular degeneration.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region.bioRxiv : the preprint server for biology · 2025Article
- Select Azo Compounds Post-translationally Modulate HTRA1 Abundance and Activity Potentially through Interactions at the Trimer Interface.ACS chemical biology · 2025Article
- Genomic Insights into Dementia: Precision Medicine and the Impact of Gene-Environment Interaction.Aging and disease · 2024Review
- An Association between HTRA1 and TGF-βJournal of clinical medicine · 2024Article
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- CRISPR editing demonstrates rs10490924 raised oxidative stress in iPSC-derived retinal cells from patients withProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2023Review
- Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases.Saudi journal of biological sciences · 2022Review
- Small Vessel Disease: Ancient Description, Novel Biomarkers.International journal of molecular sciences · 2022Review
- Review
- Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration.Experimental eye research · 2021Review
- Associations ofClinical ophthalmology (Auckland, N.Z.) · 2021Article
- The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization.Frontiers in molecular neuroscience · 2020Article
- Proteome and Secretome Dynamics of Human Retinal Pigment Epithelium in Response to Reactive Oxygen Species.Scientific reports · 2019Article
- Transient acceleration of autophagic degradation by pharmacological Nrf2 activation is important for retinal pigment epithelium cell survival.Redox biology · 2018Article
- Cerebral Small Vessel Disease: A Review Focusing on Pathophysiology, Biomarkers, and Machine Learning Strategies.Journal of stroke · 2018Article
- HtrA1 Mediated Intracellular Effects on Tubulin Using a Polarized RPE Disease Model.EBioMedicine · 2018Article
- Proteolytic Degradation and Inflammation Play Critical Roles in Polypoidal Choroidal Vasculopathy.The American journal of pathology · 2017Article
- Specific correlation between the major chromosome 10q26 haplotype conferring risk for age-related macular degeneration and the expression ofMolecular vision · 2017Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dry age-related macular degeneration (AMD) accounts for over 85% of AMD cases in the United States, whereas Japanese AMD patients predominantly progress to wet AMD or polypoidal choroidal vasculopathy. Recent genome-wide association studies have revealed a strong association between AMD and an insertion/deletion sequence between the ARMS2 (age-related maculopathy susceptibility 2) and HTRA1 (high temperature requirement A serine peptidase 1) genes. Transcription regulator activity was localized in mouse retinas using heterozygous HtrA1 knock-out mice in which HtrA1 exon 1 was replaced with β-galactosidase cDNA, thereby resulting in dominant expression of the photoreceptors. The insertion/deletion sequence significantly induced HTRA1 transcription regulator activity in photoreceptor cell lines but not in retinal pigmented epithelium or other cell types. A deletion construct of the HTRA1 regulatory region indicated that potential transcriptional suppressors and activators surround the insertion/deletion sequence. Ten double-stranded DNA probes for this region were designed, three of which interacted with nuclear extracts from 661W cells in EMSA. Liquid chromatography-mass spectrometry (LC-MS/MS) of these EMSA bands subsequently identified a protein that bound the insertion/deletion sequence, LYRIC (lysine-rich CEACAM1 co-isolated) protein. In addition, induced pluripotent stem cells from wet AMD patients carrying the insertion/deletion sequence showed significant up-regulation of the HTRA1 transcript compared with controls. These data suggest that the insertion/deletion sequence alters the suppressor and activator cis-elements of HTRA1 and triggers sustained up-regulation of HTRA1. These results are consistent with a transgenic mouse model that ubiquitously overexpresses HtrA1 and exhibits characteristics similar to those of wet AMD patients.
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