ArticleThe American journal of pathology2015
Hematopoietic tissue factor-protease-activated receptor 2 signaling promotes hepatic inflammation and contributes to pathways of gluconeogenesis and steatosis in obese mice.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.BioMed research international · 2016Pooled it
- Coagulation protease-activated receptor-2 (PAR2) promotes dyslipidemia, obesity and MASLD through repression of the hepatic pioneer factor HNF4α.JHEP reports : innovation in hepatology · 2026Article
- Macrophage Plg-RJournal of thrombosis and haemostasis : JTH · 2026Article
- Senescence-related gene signatures in Crohn's disease: integrating bulk and single-cell RNA sequencing analysis.Scientific reports · 2025Article
- The Role of PAR2 in MASLD Progression and HCC Development.International journal of molecular sciences · 2025Review
- 1-Piperidine Propionic Acid Protects from Septic Shock Through Protease Receptor 2 Inhibition.International journal of molecular sciences · 2024Article
- Yam Gruel alone and in combination with metformin regulates hepatic lipid metabolism disorders in a diabetic rat model by activating the AMPK/ACC/CPT-1 pathway.Lipids in health and disease · 2024Article
- Xa inhibitor edoxaban ameliorates hepatic ischemia-reperfusion injury via PAR-2-ERK 1/2 pathway.PloS one · 2024Article
- Reply.Hepatology (Baltimore, Md.) · 2023Article
- Article
- Life without Proteinase Activated Receptor 2 (PAR2) Alters Body Composition and Glucose Tolerance in Mice.Nutrients · 2022Article
- Mechanism of Lipid Accumulation through PAR2 Signaling in Diabetic Male Mice.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- Macrophage protease-activated receptor 2 regulates fetal liver erythropoiesis in mice.Blood advances · 2020Article
- Unique transcriptional signatures of sleep loss across independently evolved cavefish populations.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2020Article
- Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2.International journal of molecular sciences · 2020Article
- PAR2 controls cholesterol homeostasis and lipid metabolism in nonalcoholic fatty liver disease.Molecular metabolism · 2019Article
- FoxO6-mediated IL-1β induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice.Redox biology · 2019Article
- Roles of Coagulation Proteases and PARs (Protease-Activated Receptors) in Mouse Models of Inflammatory Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Tissue factor: newer concepts in thrombosis and its role beyond thrombosis and hemostasis.Cardiovascular diagnosis and therapy · 2018Review
- TCR-pMHC encounter differentially regulates transcriptomes of tissue-resident CD8 T cells.European journal of immunology · 2018Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Failure to inhibit hepatic gluconeogenesis is a major mechanism contributing to fasting hyperglycemia in type 2 diabetes and, along with steatosis, is the hallmark of hepatic insulin resistance. Obesity is associated with chronic inflammation in multiple tissues, and hepatic inflammation is mechanistically linked to both steatosis and hepatic insulin resistance. Here, we delineate a role for coagulation signaling via tissue factor (TF) and proteinase-activated receptor 2 (PAR2) in obesity-mediated hepatic inflammation, steatosis, and gluconeogenesis. In diet-induced obese mice, TF tail signaling independent of PAR2 drives CD11b(+)CD11c(+) hepatic macrophage recruitment, and TF-PAR2 signaling contributes to the accumulation of hepatic CD8(+) T cells. Transcripts of key pathways of gluconeogenesis, lipogenesis, and inflammatory cytokines were reduced in high-fat diet-fed mice that lack the cytoplasmic domain of TF (F3) (TF(ΔCT)) or that are deficient in PAR2 (F2rl1), as well as by pharmacological inhibition of TF-PAR2 signaling in diet-induced obese mice. These gluconeogenic, lipogenic, and inflammatory pathway transcripts were similarly reduced in response to genetic ablation or pharmacological inhibition of TF-PAR2 signaling in hematopoietic cells and were mechanistically associated with activation of AMP-activated protein kinase (AMPK). These findings indicate that hematopoietic TF-PAR2 signaling plays a pivotal role in the hepatic inflammatory responses, steatosis, and hepatic insulin resistance that lead to systemic insulin resistance and type 2 diabetes in obesity.
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