ArticleInternational wound journal2021
Endoplasmic reticulum stress in human chronic wound healing: Rescue by 4-phenylbutyrate.
Article in International wound journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting endoplasmic reticulum stress to attenuate cisplatin resistance in non-small cell lung cancer.Medical oncology (Northwood, London, England) · 2026Article
- Article
- PERK protein kinase facilitates keratinocyte collective cell migration by engagement with cell adhesion molecules, independent of its kinase activity.Molecular biology of the cell · 2025Article
- Hydroxyurea induces an oxidative stress response that triggers ER expansion and cytoplasmic protein aggregation.PLoS biology · 2025Article
- Potential roles of histone deacetylases in diabetic wound healing.World journal of diabetes · 2025Review
- Collaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- Wound management, healing, and early prosthetic rehabilitation: Part 3 - A scoping review of chemical biomarkers.Canadian prosthetics & orthotics journal · 2025Review
- Cellular and molecular roles of reactive oxygen species in wound healing.Communications biology · 2024Review
- Ultrastructural and immunohistochemical evaluation of hyperplastic soft tissues surrounding dental implants in fibular jaws.Scientific reports · 2024Article
- Role of the mitochondrial protein cyclophilin D in skin wound healing and collagen secretion.JCI insight · 2024Article
- Wound management, healing, and early prosthetic rehabilitation: Part 1 - A scoping review of healing and non-healing definitions.Canadian prosthetics & orthotics journal · 2024Review
- The cGAS-STING pathway: a therapeutic target in diabetes and its complications.Burns & trauma · 2024Review
- Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.BMC oral health · 2023Article
- Multifaceted roles of mitochondria in wound healing and chronic wound pathogenesis.Frontiers in cell and developmental biology · 2023Review
- Calreticulin: a multifunctional protein with potential therapeutic applications for chronic wounds.Frontiers in medicine · 2023Review
- Potential Clinical Applications of the Postbiotic Butyrate in Human Skin Diseases.Molecules (Basel, Switzerland) · 2022Review
- New Insights on the Effects of Dietary Omega-3 Fatty Acids on Impaired Skin Healing in Diabetes and Chronic Venous Leg Ulcers.Foods (Basel, Switzerland) · 2021Review
- Collagen's enigmatic, highly conservedProceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
During wound healing, cells have a high rate of protein synthesis and many proteins need to be folded post-translationally to function, which occurs in the endoplasmic reticulum (ER). In addition to proliferation, several cellular stress conditions, such as hypoxia, in the wound micro-environment lead to the accumulation of unfolded or misfolded proteins in the ER, causing ER stress. Eukaryotic cells have a signalling system to manage ER stress called the unfolded protein response (UPR). Mild UPR activation has a beneficial homeostatic effect; however, excessive UPR induces cell death. Herein, we examined venous leg ulcer biopsies versus normal acute incisional wounds in age-matched elderly subjects and found a large increase in ER stress markers. To study the underlying mechanism, we established several cell cultures from amputated legs from the elderly that showed inherent ER stress. While both keratinocytes and fibroblasts migration was impaired by ER stress, migration of elderly leg skin keratinocytes was markedly improved after treatment with the chemical chaperone and clinically established drug 4-phenylbutyrate (4-PBA) and demonstrated a reduction in ER stress markers. In a full-thickness human skin wound healing model, 4-PBA improved the reepithelialisation rate, which suggests it as a promising drug repurposing candidate for wound healing.
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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.