ArticleThe Journal of biological chemistry2014
Proteinase-activated receptor 2 (PAR2) decreases apoptosis in colonic epithelial cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- 1-Piperidine Propionic Acid Inhibits PAR2/SerpinB3 Signaling and Reduces Glioblastoma Tumor Aggressiveness.International journal of molecular sciences · 2026Article
- Pharmacologic Modulation of the PAR-2-ERK Axis by Statins Converts Inflammatory Survival Signalling into Apoptosis in Colorectal Cancer Cells.International journal of molecular sciences · 2026Article
- A mast cell-associated apoptosis-related transcriptomic signature in clear cell renal cell carcinoma andFrontiers in immunology · 2026Article
- Article
- Targeting PAR-2-driven inflammatory pathways in colorectal cancer: mechanistic insights from atorvastatin and rosuvastatin treatment in cell line models.Translational cancer research · 2025Article
- A New Strategy in Modulating the Protease-Activated Receptor 2 (Par2) in Autoimmune Diseases.International journal of molecular sciences · 2025Review
- Tissue Kallikrein-1 Suppresses Type I Interferon Responses and Reduces Depressive-Like Behavior in the MRL/lpr Lupus-Prone Mouse Model.International journal of molecular sciences · 2024Article
- Protease-activated receptor 2 attenuates doxorubicin-induced apoptosis in colon cancer cells.Journal of cell communication and signaling · 2023Article
- PARs in the inflammation-cancer transformation of CRC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Edoxaban, a Factor Xa-Specific Direct Oral Anticoagulant, Significantly Suppresses Tumor Growth in Colorectal Cancer Colon26-Inoculated BALB/c Mice.TH open : companion journal to thrombosis and haemostasis · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Critical roles of G protein-coupled receptors in regulating intestinal homeostasis and inflammatory bowel disease.Mucosal immunology · 2022Review
- Blockage of protease-activated receptor 2 exacerbates inflammation in high-fat environment partly through autophagy inhibition.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- PAR2 Deficiency Induces Mitochondrial ROS Generation and Dysfunctions, Leading to the Inhibition of Adipocyte Differentiation.Oxidative medicine and cellular longevity · 2021Article
- Protease-Activated Receptors - Key Regulators of Inflammatory Bowel Diseases Progression.Journal of inflammation research · 2021Review
- Expression of Proteinase-Activated Receptor 2 During Colon Volvulus in the Horse.Frontiers in veterinary science · 2020Article
- Treatment of Pulpectomized Teeth With Trypsin Prior to Transplantation of Mobilized Dental Pulp Stem Cells Enhances Pulp Regeneration in Aged Dogs.Frontiers in bioengineering and biotechnology · 2020Article
- Proteinase‑activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury.Molecular medicine reports · 2019Article
- Triple-negative breast cancer-derived microvesicles transfer microRNA221 to the recipient cells and thereby promote epithelial-to-mesenchymal transition.The Journal of biological chemistry · 2019Article
- PAR2 Inhibition Enhanced the Sensitivity of Colorectal Cancer Cells to 5-FU and Reduced EMT Signaling.Oncology research · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucosal biopsies from inflamed colon of inflammatory bowel disease patients exhibit elevated epithelial apoptosis compared with those from healthy individuals, disrupting mucosal homeostasis and perpetuating disease. Therapies that decrease intestinal epithelial apoptosis may, therefore, ameliorate inflammatory bowel disease, but treatments that specifically target apoptotic pathways are lacking. Proteinase-activated receptor-2 (PAR2), a G protein-coupled receptor activated by trypsin-like serine proteinases, is expressed on intestinal epithelial cells and stimulates mitogenic pathways upon activation. We sought to determine whether PAR2 activation and signaling could rescue colonic epithelial (HT-29) cells from apoptosis induced by proapoptotic cytokines that are increased during inflammatory bowel disease. The PAR2 agonists 2-furoyl-LIGRLO (2f-LI), SLIGKV and trypsin all significantly reduced cleavage of caspase-3, -8, and -9, poly(ADP-ribose) polymerase, and the externalization of phosphatidylserine after treatment of cells with IFN-γ and TNF-α. Knockdown of PAR2 with siRNA eliminated the anti-apoptotic effect of 2f-LI and increased the sensitivity of HT-29 cells to cytokine-induced apoptosis. Concurrent inhibition of both MEK1/2 and PI3K was necessary to inhibit PAR2-induced survival. 2f-LI was found to increase phosphorylation and inactivation of pro-apoptotic BAD at Ser(112) and Ser(136) by MEK1/2 and PI3K-dependent signaling, respectively. PAR2 activation also increased the expression of anti-apoptotic MCL-1. Simultaneous knockdown of both BAD and MCL-1 had minimal effects on PAR2-induced survival, whereas single knockdown had no effect. We conclude that PAR2 activation reduces cytokine-induced epithelial apoptosis via concurrent stimulation of MEK1/2 and PI3K but little involvement of MCL-1 and BAD. Our findings represent a novel mechanism whereby serine proteinases facilitate epithelial cell survival and may be important in the context of colonic healing.
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