ArticleScience translational medicine2015
The proinflammatory role of HECTD2 in innate immunity and experimental lung injury.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04359290 (Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS A Single-arm, Open-label, Proof of Concept Study), which is not on this map. Cited by 37 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.
Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS A Single-arm, Open-label, Proof of Concept Study
Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
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- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- Localised delivery of interleukin-13 from a PLGA microparticle embedded GelMA hydrogel improves functional and histopathological recovery in a mouse contusion spinal cord injury model.Bioactive materials · 2025Article
- Inhibition of virally induced TFEB proteasomal degradation as a host-centric therapeutic approach for coronaviral infection.Science advances · 2025Article
- Rare loss-of-function variants in HECTD2 and AKAP11 confer risk of bipolar disorder.Nature genetics · 2025Article
- Expression of HECTD2 predicts peritoneal metastasis of gastric cancer and reconstructs immune microenvironment.Cancer cell international · 2024Article
- HECTD2 as a target for veratric acid in the regulation of ferroptosis in renal cell carcinoma.Amino acids · 2024Article
- NRIP1 aggravates lung injury caused byAging · 2022Article
- Liver and Kidney Surgical Anatomy to Verify the Effect of miR-221 on Organ Damage in Septic Rats.Journal of healthcare engineering · 2022Article
- Identification of transcriptional regulatory network associated with response of host epithelial cells to SARS-CoV-2.Scientific reports · 2021Article
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- HIF-1α Induces HECTD2 Up-Regulation and Aggravates the Malignant Progression of Renal Cell CancerFrontiers in cell and developmental biology · 2021Article
- Recent updates on COVID-19: A holistic review.Heliyon · 2020Review
- A small molecule NRF2 activator BC-1901S ameliorates inflammation through DCAF1/NRF2 axis.Redox biology · 2020Article
- Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species.Molecular medicine reports · 2020Article
- Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2020Article
- The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity.JCI insight · 2020Article
- Neuronal Wiskott-Aldrich syndrome protein regulates Pseudomonas aeruginosa-induced lung vascular permeability through the modulation of actin cytoskeletal dynamics.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Toll-like Receptor 8 Stability Is Regulated by Ring Finger 216 in Response to Circulating MicroRNAs.American journal of respiratory cell and molecular biology · 2020Article
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13 authors at 1 institution in 1 country.
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Abstract
Invading pathogens may trigger overactivation of the innate immune system, which results in the release of large amounts of proinflammatory cytokines (cytokine storm) and leads to the development of pulmonary edema, multiorgan failure, and shock. PIAS1 is a multifunctional and potent anti-inflammatory protein that negatively regulates several key inflammatory pathways such as Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor κB (NF-κB). We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. We also identified a mislocalized HECTD2 polymorphism, HECTD2(A19P), that was present in 8.5% of the population and functioned to reduce inflammation. This polymorphism prevented HECTD2/PIAS1 nuclear interaction, thus preventing PIAS1 degradation. The HECTD2(A19P) polymorphism was also protective toward acute respiratory distress syndrome (ARDS). We then developed a small-molecule inhibitor, BC-1382, that targeted HECTD2 and attenuated lipopolysaccharide (LPS)- and Pseudomonas aeruginosa-induced lung inflammation. These studies describe an unreported innate immune pathway and suggest that mutation or antagonism of the E3 ligase HECTD2 results in reduced severity of lung inflammation by selectively modulating the abundance of the anti-inflammatory protein PIAS1.
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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.