Increased gelsolin expression and retarded collagen lattice contraction with smooth muscle cells from Crohn's diseased intestine.
Intestinal smooth muscle cells (SMC) produce the fibrotic tissue, strictures, that characterize Crohn's disease. These SMC change their phenotype from a contractile muscle form to an inflammation-responsive form that migrates and synthesizes a collagen matrix. It is postulated that the inflammatory responsive SMC form associates differently with its surrounding collagen matrix compared to the normal SMC form. SMC derived from Crohn's diseased and uninvolved bowel were sustained in cell culture. Cultured SMC incorporated in collagen lattices have the capacity to reduce the size of that lattice, referred to as lattice contraction. At day 2, Crohn's SMC-populated collagen lattices were reduced to 21% of their initial area, while non-Crohn's SMC collagen lattices were reduced to 8%. Crohn's SMC demonstrate retarded lattice contraction compared to non-Crohn's SMC. When grown in monolayer culture, Crohn's-derived SMC cover 30% more area than non-Crohn's SMC. By Western blot analysis Crohn's SMC express more gelsolin, an actin-binding protein found elevated in cells exhibiting increased cell motility. Was the increased expression of gelsolin related to retarded collagen lattice contraction? Intracellular levels of gelsolin were elevated by the electroporation of plasma gelsolin protein into suspended non-Crohn's SMC. When incorporated in collagen lattices, gelsolin loaded cells showed retarded lattice contraction compared to SMC loaded with albumin. Crohn's SMC show increased expression of gelsolin, which may be associated with a diminished capacity to reorganize collagen fiber bundles. It is suggested that increased concentrations of gelsolin in Crohn's SMC is consistent with enhanced cell migration as a consequence of the inflammatory state of Crohn's diseased intestine.
Ehrlich
H P
HP
Section of Plastic and Reconstrutive Surgery, Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, USA. pehrlich@psu.edu
Allison
G M
GM
Page
M J
MJ
Kolton
W A
WA
Graham
M
M
D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D018260:Gelsolin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D018260:Gelsolin; D003094:Collagen