ArticleThe American journal of pathology2021
Hypoxia and Hypoxia-Inducible Factor-1α Regulate Endoplasmic Reticulum Stress in Nucleus Pulposus Cells: Implications of Endoplasmic Reticulum Stress for Extracellular Matrix Secretion.
Article in The American journal of pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 36 citations in OpenAlex.
- ANGII Initiated HSF2 Trans-Activating HIF-1α Through Induction of ER Stress to Promote Cardiac Hypertrophy.Clinical and experimental pharmacology & physiology · 2026Article
- Review
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- A Cu-based metal-organic framework based on desloratadine and siHIF-1α for achievement of genes/drugs/CDT combination therapy in hepatocellular carcinoma.Journal of nanobiotechnology · 2026Article
- Stress-response exhaustion in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026Review
- Natural products targeting programmed cell death: a novel therapeutic strategy for intervertebral disc degeneration.International journal of surgery (London, England) · 2026Review
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- Transcriptomic and Functional Comparison of Cells Isolated From Healthy and Degenerated Ovine Intervertebral Discs.Journal of cellular and molecular medicine · 2026Article
- 6-Shogaol Alleviates Endotoxin-Induced Uveitis via Activation of HIF-1α to Regulate Inflammatory Responses and Endoplasmic Reticulum Stress.Investigative ophthalmology & visual science · 2025Article
- Deciphering SPP1-related macrophage signaling in the pathogenesis of intervertebral disc degeneration.Cell biology and toxicology · 2025Article
- Quercetin Alleviates Hyperglycemic-Generated Endoplasmic Reticulum Stress-Contacted Apoptosis of Rat Nucleus Pulposus Cells.Balkan medical journal · 2025Article
- Rewiring tumor visibility: The immunopeptidome as a dynamic interface between antigen processing, microenvironmental stress, and immune recognition.Frontiers in oncology · 2025Review
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- Progress in the Application of Hydrogels in Intervertebral Disc Repair: A Comprehensive Review.Current pain and headache reports · 2024Review
- Role of Autophagy and Pyroptosis in Intervertebral Disc Degeneration.Journal of inflammation research · 2024Review
- The role of biomechanical factors in models of intervertebral disc degeneration across multiple length scales.APL bioengineering · 2023Review
- Identification of endoplasmic reticulum stress-related biomarkers of diabetes nephropathy based on bioinformatics and machine learning.Frontiers in endocrinology · 2023Article
- Sal003 alleviated intervertebral disc degeneration by inhibiting apoptosis and extracellular matrix degradation through suppressing endoplasmic reticulum stress pathway in rats.Frontiers in pharmacology · 2023Article
- Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment.Frontiers in immunology · 2023Review
- Activation of the integrated stress response (ISR) pathways in response to Ref-1 inhibition in human pancreatic cancer and its tumor microenvironment.Frontiers in medicine · 2023Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Endoplasmic reticulum (ER) stress is shown to promote nucleus pulposus (NP) cell apoptosis and intervertebral disc degeneration. However, little is known about ER stress regulation by the hypoxic disc microenvironment and its contribution to extracellular matrix homeostasis. NP cells were cultured under hypoxia (1% partial pressure of oxygen) to assess ER stress status, and gain-of-function and loss-of-function approaches were used to assess the role of hypoxia-inducible factor (HIF)-1α in this pathway. In addition, the contribution of ER stress induction on the NP cell secretome was assessed by a nontargeted quantitative proteomic analysis by sequential windowed data independent acquisition of the total high-resolution mass spectra-mass spectrometry. NP cells exhibited a lower ER stress burden under hypoxia. Knockdown of HIF-1α increased C/EBP homologous protein, protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) levels, whereas HIF-1α stabilization decreased the expression of ER stress markers Ddit3, Hsp5a, Atf6, and Eif2a. Interestingly, ER stress inducers tunicamycin and thapsigargin induced HIF-1α activity under hypoxia while promoting the unfolded protein response. NP cell secretome analysis demonstrated an impact of ER stress induction on extracellular matrix secretion, with decreases in collagens and cell adhesion-related proteins. Moreover, analysis of transcriptomic data of NP tissues from aged mice and degenerated human discs showed higher levels of unfolded protein response markers and decreased levels of matrix components. Our study shows, for the first time, that hypoxia and HIF-1α attenuate ER stress responses in NP cells, and ER stress promotes inefficient extracellular matrix secretion under hypoxia.
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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.