ArticleCell communication and signaling : CCS2023
Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- GATA4-Driven Transcription of HtrA1 Promotes Cellular Senescence in Ménière's Disease and Age-Related Audio-Vestibular Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ALYREF stabilizes MZF1 via m5C modification to exacerbate cardiac remodeling and atrial fibrillation in heart failure.Cellular and molecular life sciences : CMLS · 2026Article
- Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.Investigative ophthalmology & visual science · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Function ofInsects · 2026Article
- Identification of potential ferroptosis-related biomarkers in proliferative vitreoretinopathy based on machine learning.Frontiers in molecular biosciences · 2026Article
- Harnessing Natural Extracellular Vesicles to Combat Age-Related Diseases: From Aging Drivers to Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- Human papillomavirus E7 inhibits immune responses in keratinocytes by activating HTRA1‑mediated mitophagy.International journal of molecular medicine · 2026Article
- The contribution of ferroptosis to the epithelial-mesenchymal transition phenotype in models of age-related macular degeneration.Frontiers in cell and developmental biology · 2026Article
- Comprehensive bulk and single-cell RNA sequencing uncovers senescence-associated biomarkers in therapeutic mesenchymal stem cells.Scientific reports · 2025Article
- Pharmacovigilance analysis of vision disorders relating to brimonidine treatment and mechanism study using network toxicology and molecular docking.Scientific reports · 2025Article
- Optimization and Application of Seahorse Glycolytic Stress Test in Mouse Corneal Tissues: Revealing Metabolic Profiles in Injury Models.Investigative ophthalmology & visual science · 2025Article
- The Dual Role of Cellular Senescence in Macrophages: Unveiling the Hidden Driver of Age-Related Inflammation in Kidney Disease.International journal of biological sciences · 2025Review
- Differential Effect of Aldosterone or Mineralocorticoid Receptor Overexpression on Retinal Inflammation.Investigative ophthalmology & visual science · 2024Article
- Fructose vs. glucose: modulating stem cell growth and function through sugar supplementation.FEBS open bio · 2024Article
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis.Clinical interventions in aging · 2024Review
- Protective Effect and Related Mechanism of Modified Danggui Buxue Decoction on Retinal Oxidative Damage in Mice based on Network Pharmacology.Current pharmaceutical design · 2024Article
- Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis.Journal of translational medicine · 2023Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAge-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn't been investigated in the pathogenesis of AMD.
methodsWestern blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-β-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1α expression both in vitro and in vivo.
resultsIn our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO
conclusionsOur study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD. Video Abstract.
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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 Socratic graph.