ArticleHepatology (Baltimore, Md.)2022
Hepatic kinome atlas: An in-depth identification of kinase pathways in liver fibrosis of humans and rodents.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Who cites it
43 citing papers in PubMed, 46 citations in OpenAlex.
- The Human PNPLA3FASEB bioAdvances · 2026Article
- Hepatic neurons and metabolically induced liver dysfunction.Nature reviews. Endocrinology · 2026Review
- GαMetabolites · 2026Article
- Anatomical Atlas of Kinase Responsiveness to Weight Gain: Adipose Depot Reprogramming in Diet-Induced Adiposity.Metabolites · 2026Article
- Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine.The Journal of biological chemistry · 2026Article
- An Exploratory Study of Kinase Activation Profiles in Hypoxic Human Cardiomyocytes Treated with Protective Extracellular Vesicles.Research square · 2026Article
- Unmasking a neurotoxic duo: a comprehensive overview of fentanyl-xylazine crosstalk in kinase pathways.Frontiers in cellular neuroscience · 2026Article
- Nicotine combined with estrogen activates protein kinase PKCι and TAO, while inhibiting specific MAP kinase pathways in cultured human neurons: an atlas of kinase activities for nicotine use disorder.Frontiers in cellular neuroscience · 2026Article
- Discoidin Domain Receptor 1 in Colonic Epithelial Cells: A Paracrine Driver of Colonic Fibrosis.Current pharmaceutical biotechnology · 2026Article
- Bilirubin Hepatic and Intestinal Transport and Catabolism: Physiology, Pathophysiology, and Benefits.Antioxidants (Basel, Switzerland) · 2025Review
- The physiology of MASLD: molecular pathways between liver and adipose tissues.Clinical science (London, England : 1979) · 2025Review
- Fibrosis: cross-organ biology and pathways to development of innovative drugs.Nature reviews. Drug discovery · 2025Review
- Multi-Omic Analysis of Glutamate Excitotoxicity in Primary Neuronal Cultures.Journal of neurochemistry · 2025Article
- Protective effects of central leptin on whole-body energy homeostasis upon acute olanzapine exposure.bioRxiv : the preprint server for biology · 2025Article
- Developmental pyrethroid exposure disrupts molecular pathways for MAP kinase and circadian rhythms in mouse brain.Physiological genomics · 2025Article
- Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Bilirubin bioconversion to urobilin in the gut-liver-kidney axis: A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome.Metabolism: clinical and experimental · 2025Review
- Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.Clinical science (London, England : 1979) · 2025Review
- Urobilin Derived from Bilirubin Bioconversion Binds Albumin and May Interfere with Bilirubin Interacting with Albumin: Implications for Disease Pathology.Biomedicines · 2025Article
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Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsResolution of pathways that converge to induce deleterious effects in hepatic diseases, such as in the later stages, have potential antifibrotic effects that may improve outcomes. We aimed to explore whether humans and rodents display similar fibrotic signaling networks. APPROACH AND
resultsWe assiduously mapped kinase pathways using 340 substrate targets, upstream bioinformatic analysis of kinase pathways, and over 2000 random sampling iterations using the PamGene PamStation kinome microarray chip technology. Using this technology, we characterized a large number of kinases with altered activity in liver fibrosis of both species. Gene expression and immunostaining analyses validated many of these kinases as bona fide signaling events. Surprisingly, the insulin receptor emerged as a considerable protein tyrosine kinase that is hyperactive in fibrotic liver disease in humans and rodents. Discoidin domain receptor tyrosine kinase, activated by collagen that increases during fibrosis, was another hyperactive protein tyrosine kinase in humans and rodents with fibrosis. The serine/threonine kinases found to be the most active in fibrosis were dystrophy type 1 protein kinase and members of the protein kinase family of kinases. We compared the fibrotic events over four models: humans with cirrhosis and three murine models with differing levels of fibrosis, including two models of fatty liver disease with emerging fibrosis. The data demonstrate a high concordance between human and rodent hepatic kinome signaling that focalizes, as shown by our network analysis of detrimental pathways.
conclusionsOur findings establish a comprehensive kinase atlas for liver fibrosis, which identifies analogous signaling events conserved among humans and rodents.
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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.