ArticleJournal of advanced research2024
Triad3A-Mediated K48-Linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- Pterostilbene Attenuates Neuronal Ferroptosis After Traumatic Brain Injury: Involvement of the SIRT1/PGC-1α/NRF2 Signaling Pathway.Molecular neurobiology · 2026Article
- Toll-like receptor 9 arginine methylation promotes ferroptosis in prostate cancer through the NRF2/GPX4 signaling pathway.Translational andrology and urology · 2026Article
- Article
- SPSB3-mediated K48- and K63- linked ubiquitination and degradation of TUFM promote apoptosis induced by myocardial ischemia/reperfusion injury.Cell biology and toxicology · 2026Article
- NPM3 functions as a lactyltransferase to promote necroptosis in male diabetic cardiomyopathy mice models via FASN transcription modulation.Nature communications · 2026Article
- NPRL2 restricts porcine reproductive and respiratory syndrome virus replication by targeting viral Nsp1α for autophagic degradation.Veterinary research · 2026Article
- Inhibiting SHP2 improves ventricular remodeling by restoring AMPK phosphorylation and mitochondrial homeostasis.Cell communication and signaling : CCS · 2026Article
- Integrated Multi-Omics Analysis Identifies PDK4 and ACOT1 as Metabolic Hub Genes Associated With Myocardial Fibrosis in Diabetic Cardiomyopathy.Journal of diabetes research · 2026Article
- ARCN1 suppresses innate immune responses against respiratory syncytial virus by promoting STUB1-mediated IKKε degradation.PLoS pathogens · 2025Article
- Cardiomyocyte OTUD1 drives diabetic cardiomyopathy via directly deubiquitinating AMPKα2 and inducing mitochondrial dysfunction.Nature communications · 2025Article
- Distinct types of protein modifications in diabetic endothelial dysfunction.Cardiovascular diabetology · 2025Review
- Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction.Cell death & disease · 2025Article
- TRIM22 promotes glioblastoma development by ubiquitinating Bcl-2.Molecular & cellular oncology · 2025Article
- Genipin attenuates oxidative damage in periodontal tissues by alleviating mitochondrial dysfunction and abnormal glucose uptake through inhibition of UCP2.Frontiers in pharmacology · 2025Article
- HINT2 protects against pressure overload-induced cardiac remodelling through mitochondrial pathways.Journal of cellular and molecular medicine · 2024Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTargeted protein degradation represents a promising therapeutic approach, while diabetic cardiomyopathy (DCM) arises as a consequence of aberrant insulin secretion and impaired glucose and lipid metabolism in the heart..
objectivesConsidering that the Toll-like receptor 9 (TLR9) signaling pathway plays a pivotal role in regulating energy metabolism, safeguarding cardiomyocytes, and influencing glucose uptake, the primary objective of this study was to investigate the impact of TLR9 on diabetic cardiomyopathy (DCM) and elucidate its underlying mechanism.
methodsMouse model of DCM was established using intraperitoneal injection of STZ, and mice were transfected with adeno-associated virus serotype 9-TLR9 (AAV9-TLR9) to assess the role of TLR9 in DCM. To explore the mechanism of TLR9 in regulating DCM disease progression, we conducted interactome analysis and employed multiple molecular approaches.
resultsOur study revealed a significant correlation between TLR9 expression and mouse DCM. TLR9 overexpression markedly mitigated cardiac dysfunction, myocardial fibrosis, oxidative stress, and apoptosis in DCM, while inflammation levels remained relatively unaffected. Mechanistically, TLR9 overexpression positively modulated mitochondrial bioenergetics and activated the AMPK-PGC1a signaling pathway. Furthermore, we identified Triad3A as an interacting protein that facilitated TLR9's proteasomal degradation through K48-linked ubiquitination. Inhibiting Triad3A expression improved cardiac function and pathological changes in DCM by enhancing TLR9 activity.
conclusionsThe findings of this study highlight the critical role of TLR9 in maintaining cardiac function and mitigating pathological alterations in diabetic cardiomyopathy. Triad3A-mediated regulation of TLR9 expression and function has significant implications for understanding the pathogenesis of DCM. Targeting TLR9 and its interactions with Triad3A may hold promise for the development of novel therapeutic strategies for diabetic cardiomyopathy. Further research is warranted to fully explore the therapeutic potential of TLR9 modulation in the context of cardiovascular diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.