Trial reportThe Journal of biological chemistry2012
High temperature requirement factor A1 (HTRA1) gene regulates angiogenesis through transforming growth factor-β family member growth differentiation factor 6.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Association between polymorphism rs11200638 in the HTRA1 gene and the response to anti-VEGF treatment of exudative AMD: a meta-analysis.BMC ophthalmology · 2017Pooled it
- HTRA1-dependent proteolysis induces age-related retinal degeneration and exacerbates choroidal neovascularization.Disease models & mechanisms · 2025Article
- HTRA1 and complement activation in neovascular age-related macular degeneration.Japanese journal of ophthalmology · 2025Article
- Article
- An Association between HTRA1 and TGF-βJournal of clinical medicine · 2024Article
- First Trimester Placental Biomarkers for Pregnancy Outcomes.International journal of molecular sciences · 2024Review
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing.Molecular therapy. Nucleic acids · 2023Article
- HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia.Current issues in molecular biology · 2023Article
- Choroidal Neovascular Membranes in Retinal and Choroidal Tumors: Origins, Mechanisms, and Effects.International journal of molecular sciences · 2023Review
- Geographic atrophy: pathophysiology and current therapeutic strategies.Frontiers in ophthalmology · 2023Review
- TGF-β/Smad Signalling Activation by HTRA1 Regulates the Function of Human Lens Epithelial Cells and Its Mechanism in Posterior Subcapsular Congenital Cataract.International journal of molecular sciences · 2022Article
- Placental multi-omics integration identifies candidate functional genes for birthweight.Nature communications · 2022Observational
- Advances in Immunomodulation and Immune Engineering Approaches to Improve Healing of Extremity Wounds.International journal of molecular sciences · 2022Review
- Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases.Saudi journal of biological sciences · 2022Review
- Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model.The Journal of clinical investigation · 2021Article
- Article
- Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration.Experimental eye research · 2021Review
- A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- The interplay of oxidative stress and ARMS2-HTRA1 genetic risk in neovascular AMD.Vessel plus · 2021Article
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
Genome-wide association study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 has been reported to interact with members of the transforming growth factor-β (TGF-β) family and regulate their signaling pathways. Growth differentiation factor 6 (GDF6), a member of the TGF-β family, is involved in ectoderm patterning and eye development. Mutations in GDF6 have been associated with abnormal eye development that may result in microphthalmia and anophthalmia. In this report, we identified a single nucleotide polymorphism (SNP) rs6982567 A/G near the GDF6 gene that is significantly associated with AMD (p value = 3.54 × 10(-8)). We demonstrated that the GDF6 AMD risk allele (rs6982567 A) is associated with decreased expression of the GDF6 and increased expression of HTRA1. Similarly, the HTRA1 AMD risk allele (rs10490924 T) is associated with decreased GDF6 and increased HTRA1 expression. We observed decreased vascular development in the retina and significant up-regulation of GDF6 gene in the RPE layer, retinal and brain tissues in HTRA1 knock-out (htra1(-/-)) mice as compared with the wild-type counterparts. Furthermore, we showed enhanced SMAD signaling in htra1(-/-) mice. Our data suggests a critical role of HTRA1 in the regulation of angiogenesis via TGF-β signaling and identified GDF6 as a novel disease gene for AMD.
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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.