Proliferation, not apoptosis, alters epithelial cell migration in small intestine of CFTR null mice.
Expression of a mutated cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to enhance proliferation within CF airways, and cells expressing a mutated CFTR have been shown to be less susceptible to apoptosis. Because the CFTR is expressed in the epithelial cells lining the gastrointestinal tract and all CF mouse models are characterized by gastrointestinal obstruction, we hypothesized that CFTR null mice would have increased epithelial cell proliferation and reduced apoptosis within the small intestine. The rate of intestinal epithelial cell migration from crypt to villus was increased in CFTR null mice relative to mice expressing the wild-type CFTR. This difference in migration could be explained by an increase in epithelial cell proliferation but not by a difference in apoptosis within the crypts of Lieberkühn. In addition, using two independent sets of CF cell lines, we found that epithelial cell susceptibility to apoptosis was unrelated to the presence of a functional CFTR. Thus increased proliferation but not alterations in apoptosis within epithelial cells might contribute to the pathophysiology of CF.
Gallagher
A M
AM
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Gottlieb
R A
RA
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D005720:Gamma Rays; D007421:Intestine, Small / Q000473:pathology* / Q000528:radiation effects; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D018181:Mice, Inbred CFTR; D014466:Ultraviolet Rays
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001973:Bromodeoxyuridine