ArticlePloS one2017
Apoptosis signal-regulating kinase 1 inhibition attenuates cardiac hypertrophy and cardiorenal fibrosis induced by uremic toxins: Implications for cardiorenal syndrome.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 34 citations in OpenAlex.
- The Heart-Kidney Axis in Heart Failure and Chronic Kidney Disease: Mechanisms, Mediators, and Therapeutic Implications.Biomolecules · 2026Review
- An Integrated Therapeutic Strategy for Cardiorenal Syndrome to Target Oxidative Stress, Inflammation, and Fibrosis.Reviews in cardiovascular medicine · 2026Review
- Chronic kidney disease-associated cardiomyopathy: clinical features, pathophysiology and treatment.Nature reviews. Cardiology · 2026Review
- Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies.Acta pharmacologica Sinica · 2025Review
- Gut-Heart Axis: The Role of Gut Microbiota and Metabolites in Heart Failure.Circulation research · 2025Review
- Gene Expression Profile of Cultured Human Coronary Arterial Endothelial Cells Exposed to Serum from Chronic Kidney Disease Patients: Role ofInternational journal of molecular sciences · 2025Article
- Renal organic anion transporter 1: clinical relevance and the underlying mechanisms in chronic kidney disease.BMC nephrology · 2025Review
- Current Perspectives on the NF-κB Signaling Axis as a Potential Pharmacological Target in Cardiorenal Syndrome.Drug design, development and therapy · 2025Review
- Cardiorenal Syndrome: A Literature Review.Cureus · 2023Review
- Puerarin Attenuates High-Glucose and High-Lipid-Induced Inflammatory Injury in H9c2 Cardiomyocytes via CAV3 Protein Upregulation.Journal of inflammation research · 2023Article
- Role of the Gut Microbiome in Skeletal Muscle Physiology and Pathophysiology.Current osteoporosis reports · 2022Review
- Uremic toxins in chronic kidney disease highlight a fundamental gap in understanding their detrimental effects on cardiac electrophysiology and arrhythmogenesis.Acta physiologica (Oxford, England) · 2022Review
- Research progress on the relationship between IS and kidney disease and its complications.International urology and nephrology · 2022Review
- Cathepsin K Deficiency Prevented Kidney Damage and Dysfunction in Response to 5/6 Nephrectomy Injury in Mice With or Without Chronic Stress.Hypertension (Dallas, Tex. : 1979) · 2022Article
- The Role of Gut-Derived, Protein-Bound Uremic Toxins in the Cardiovascular Complications of Acute Kidney Injury.Toxins · 2022Review
- Biomarkers in Cardiorenal Syndrome.Journal of clinical medicine · 2021Review
- Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis.Scientific reports · 2021Article
- Conditioned medium from adipose-derived stem cells attenuates ischemia/reperfusion-induced cardiac injury through the microRNA-221/222/PUMA/ETS-1 pathway.Theranostics · 2021Article
- Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome.Frontiers in pharmacology · 2021Article
- Indoxyl Sulfate Contributes to Adipose Tissue Inflammation through the Activation of NADPH Oxidase.Toxins · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular accumulation of protein-bound uremic toxins in the setting of cardiorenal syndrome leads to adverse effects on cardiorenal cellular functions, where cardiac hypertrophy and cardiorenal fibrosis are the hallmarks. In this study, we sought to determine if Apoptosis Signal-Regulated Kinase 1 (ASK1), an upstream regulator of cellular stress response, mediates cardiac hypertrophy and cardiorenal fibrosis induced by indoxyl sulfate (IS) and p-cresol sulfate (PCS) in vitro, and whether ASK1 inhibition is beneficial to ameliorate these cellular effects. PCS augmented cardiac myocyte hypertrophy and fibroblast collagen synthesis (as determined by 3H-leucine and 3H-proline incorporation, respectively), similar to our previous finding with IS. IS and PCS also increased collagen synthesis of proximal tubular cells and renal mesangial cells. Pro-hypertrophic (α-skeletal muscle actin and β-MHC) and pro-fibrotic genes (TGF-β1 and ctgf) were induced by both IS and PCS. Western blot analyses revealed the activation of ASK1 and downstream mitogen activated protein kinases (MAPKs) (p38MAPK and ERK1/2) as well as nuclear factor-kappa B (NF-κB) by IS and PCS. ASK1, OAT1/3, ERK1/2 and p38MAPK inhibitors suppressed all these effects. In summary, IS and PCS exhibit pro-hypertrophic and pro-fibrotic properties, at least in part, via the activation of ASK1 and its downstream pathways. ASK1 inhibitor is an effective therapeutic agent to alleviate protein-bound uremic toxin-induced cardiac hypertrophy and cardiorenal fibrosis in vitro, and may be translated further for cardiorenal syndrome therapy.
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.