Background: Migration of colonic lamina propria fibroblasts (CLPF) is an important mechanism during wound healing in inflammatory bowel disease (IBD). The concentration of prostaglandin E2 (PGE2) is increased in the intestinal mucosa of IBD patients. We therefore investigated the role of PGE2 in CLPF migration.
Methods: Primary cultures of CLPF were isolated from healthy controls and Crohn's disease patients. Migration assays were performed in the Boyden chamber and scratch assays. EP receptors, PGE2, intracellular cyclic adenosine monophosphate (cAMP), expression and distribution of F-actin, alpha-smooth muscle actin (SMA), and myosin light chain (MLC) were determined by immunoblotting, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA).
Results: All four EP receptor subtypes were present on CLPF. PGE2 and agonists to the EP2 and EP4 receptor reduced the migration of CLPF. Blockade of the EP2 and the EP4 receptor inhibited the effect of PGE2 on CLPF migration. An increase in intracellular cAMP reduced CLPF migration. PGE2 increased the concentrations of cAMP in CLPF, with abrogation after addition of EP2 and EP4 receptor antagonists. PGE2 and forskolin decreased the expression of alpha-SMA and F-actin and reduced cell polarization and lamellipodium formation in a scratch assay. In addition, forskolin reduced the phosphorylation of MLC (pMLC) and led to lack of accumulation of pMLC in the leading edge of CLPF.
Conclusions: PGE2 reduced the migration of CLPF via elevation of intracellular cAMP. Potential mechanisms are changes in expression of cytoskeletal proteins, failure of CLPF to polarize, and a decreased amount of pMLC. This might be a possible reason for the impairment of intestinal wound healing in IBD.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/ibd.21255 | DOI Listing |
Int J Mol Sci
December 2024
Department of Physiology and Cell Biology, School of Medicine, University of Nevada Reno, Reno, NV 89557, USA.
The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5'-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other's mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders.
View Article and Find Full Text PDFJ Med Chem
January 2025
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
The development of dual prostaglandin E receptors 2/4 (EP2/EP4) antagonists represents an attractive strategy for cancer immunotherapy. Herein, a series of 4,7-dihydro-5-thieno[2,3-]pyran derivatives with potent EP2/EP4 dual antagonism were discovered by fine-tuned structural modifications. The biphenyl side chain was found to be the key pharmacophore for the transition from EP4 antagonism to EP2/EP4 dual antagonism.
View Article and Find Full Text PDFEnviron Microbiol
December 2024
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Oxylipin signalling is central in biology, mediating processes such as cellular homeostasis, inflammation and molecular signalling. It may also facilitate inter-partner communication in the cnidarian-dinoflagellate symbiosis, though this aspect remains understudied. In this study, four oxylipin receptors were characterised using immunohistochemistry and immunoblotting in the sea anemone Exaiptasia diaphana ('Aiptasia'): Prostaglandin E2 receptor 2 (EP2) and 4 (EP4), Transient Receptor Potential cation channel A1 (TRPA1) and Glutamate Receptor Ionotropic, Kainate 2 (GRIK2).
View Article and Find Full Text PDFCell Signal
February 2025
Division of Cell Signalling and Immunology, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address:
The EP4 (prostaglandin E2) receptor plays a crucial role in myogenesis and skeletal muscle regeneration, yet its involvement in regulating insulin-dependent metabolic pathways is not well characterised. Our research investigates the expression of EP4 in rat skeletal L6 myotubes and its impact on insulin signalling. We found that activation of EP4 by selective agonists disrupts insulin signalling and insulin-stimulated glucose uptake.
View Article and Find Full Text PDFCell Rep
November 2024
Institute of Molecular Immunology, School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany. Electronic address:
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!