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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, OBJECTIVE, METHODS, RESULTS. Meshes: Antibodies, Blocking, Blotting, Western, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Epithelium, Humans, Interleukin-1beta, Oligopeptides, Peritoneum, Plasminogen Activator Inhibitor 1, Primary Cell Culture, Real-Time Polymerase Chain Reaction, Receptor, PAR-1, Reverse Transcriptase Polymerase Chain Reaction, Serum Albumin, Thrombin, Time Factors, Up-Regulation, Vascular Endothelial Growth Factor A.
user
Does pAR-1 mediate the thrombin-induced mesothelial cell overproduction of VEGF and PAI-1? Context: Thrombin mediates an excess in the production of neoangiogenetic (VEGF) and profibrotic (PAI-1) factors in human peritoneal mesothelial cells (HMC). The mechanisms leading to this overproduction have not been elucidated so far; in the context of peritoneal dialysis it can result in impaired peritoneal membrane function. This study was performed to evaluate the presence of the thrombin receptor protease-activated receptor-1 (PAR-1) in HMC and to characterize its function in the thrombin-dependent effects mentioned above. All experiments were performed using cultured primary HMC. Real-Time PCR and Western Blot were used to evaluate PAR-1; ELISA and Real-Time PCR were employed to examine PAR-1 effects on target mediators. We found that cultivated primary HMC show a basal presence of PAR-1. Stimulation with IL-1β induced an increase of the mesothelial PAR-1 expression whereas stimulation with glycosilated human serum albumin or the ligand thrombin itself resulted in decreased PAR-1 expression. Stimulation with the specific PAR-1 ligand TFLLR-NH(2) caused increased VEGF and PAI-1 levels similar to stimulation with thrombin, whereas preincubation with PAR-1 blocking antibodies ATAP2 and WEDE15 attenuated the thrombin-induced overproduction of VEGF and PAI-1.
assistant
HMC express PAR-1 and the receptor is involved in thrombin effects on these cells. These findings may be a basis for pharmacological prevention of neoangiogenesis and adhesions in the context of peritoneal dialysis and peritonitis. Final Decision: yes