Growth factor regulation of prostaglandin-endoperoxide synthase 2 (Ptgs2) expression in colonic mesenchymal stem cells.
We previously found that a population of colonic stromal cells that constitutively express high levels of prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as Cox-2) altered their location in the lamina propria in response to injury in a Myd88-dependent manner (Brown, S. L., Riehl, T. E., Walker, M. R., Geske, M. J., Doherty, J. M., Stenson, W. F., and Stappenbeck, T. S. (2007) J. Clin. Invest. 117, 258-269). At the time of this study, the identity of these cells and the mechanism by which they expressed high levels of Ptgs2 were unknown. Here we found that these colonic stromal cells were mesenchymal stem cells (MSCs). These colonic MSCs expressed high Ptgs2 levels not through interaction with bacterial products but instead as a consequence of mRNA stabilization downstream of Fgf9 (fibroblast growth factor 9), a growth factor that is constitutively expressed by the intestinal epithelium. This stabilization was mediated partially through a mechanism involving endogenous CUG-binding protein 2 (CUGbp2). These studies suggest that Fgf9 is an important factor in the regulation of Ptgs2 in colonic MSCs and may be a factor involved in its constitutive expression in vivo.
Walker
Monica R
MR
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Brown
Sarah L
SL
Riehl
Terrence E
TE
Stenson
William F
WF
Stappenbeck
Thaddeus S
TS
D000818:Animals; D000067878:CELF Proteins; D002460:Cell Line; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D051525:Fibroblast Growth Factor 9 / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D000067878:CELF Proteins; C117363:CELF2 protein, human; D051525:Fibroblast Growth Factor 9; D005419:Flavonoids; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051546:Cyclooxygenase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one