ArticleFrontiers in immunology2021
Dynamic Regulation of the Nexus Between Stress Granules, Roquin, and Regnase-1 Underlies the Molecular Pathogenesis of Warfare Vesicants.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Emulsome-Based Nanocarrier System for Controlled 4-Phenylbutyric Acid Delivery and Mechanistic Mitigation of Arsenical-Induced Skin Injury via Foam Application.Pharmaceutics · 2025Article
- Sustained delivery of 4-phenylbutyric acid via chitosan nanoparticles in foam for decontamination and treatment of lewisite-mediated skin injury.International journal of pharmaceutics · 2025Article
- Perillaldehyde Improves Parkinson-Like Deficits by Targeting G3BP Mediated Stress Granule Assembly in Preclinical Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.American journal of physiology. Renal physiology · 2025Article
- Common molecular profile of multiple structurally distinct warfare arsenicals in causing cutaneous chemical vesicant injury.Scientific reports · 2025Article
- Enhancing topical delivery of ISRIB: Optimizing cream formulations with chemical enhancers and pH adjustment.International journal of pharmaceutics · 2024Article
- HSP90, a Common Therapeutic Target for Suppressing Skin Injury Caused by Exposure to Chemically Diverse Classes of Blistering Agents.The Journal of pharmacology and experimental therapeutics · 2024Article
- Effects ofInternational journal of molecular sciences · 2023Article
- Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants.Experimental eye research · 2023Article
- Proteomic profiling of eIF3a conditional knockout mice.Frontiers in molecular biosciences · 2023Article
- Role of hair follicles in the pathogenesis of arsenical-induced cutaneous damage.Annals of the New York Academy of Sciences · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The use of chemical warfare agents is prohibited but they have been used in recent Middle Eastern conflicts. Their accidental exposure (e.g. arsenical lewisite) is also known and causes extensive painful cutaneous injury. However, their molecular pathogenesis is not understood. Here, we demonstrate that a nexus of stress granules (SGs), integrated stress, and RNA binding proteins (RBPs) Roquin and Reganse-1 play a key role. Lewisite and its prototype phenylarsine oxide (PAO) induce SG assembly in skin keratinocytes soon after exposure, which associate with various RBPs and translation-related proteins. SG disassembly was detected several hours after exposure. The dynamics of SG assembly-disassembly associates with the chemical insult and cell damage. Enhanced Roquin and Regnase-1 expression occurs when Roquin was recruited to SGs and Regnase-1 to the ribosome while in the disassembling SGs their expression is decreased with consequent induction of inflammatory mediators. SG-targeted protein translational control is regulated by the phosphorylation-dependent activation of eukaryotic initiation factors 2α (eIF2α). Treatment with integrated stress response inhibitor (ISRIB), which blocks eIF2α phosphorylation, impacted SG assembly dynamics. Topical application of ISRIB attenuated the inflammation and tissue disruption in PAO-challenged mice. Thus, the dynamic regulation of these pathways provides underpinning to cutaneous injury and identify translational therapeutic approach for these and similar debilitating chemicals.
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