Abnormal mucosal extracellular matrix deposition is associated with increased TGF-beta receptor-expressing mesenchymal cells in a mouse model of colitis.
Transforming growth factor-beta (TGF-beta) depresses mucosal inflammation and upregulates extracellular matrix (ECM) deposition. We analyzed TGF-beta receptors RI and RII as well as ECM components using the CD4(+) T-cell-transplanted SCID mouse model of colitis. The principal change in colitis was an increased proportion of TGF-beta RII(+) mucosal mesenchymal cells, predominantly alpha-smooth muscle actin (SMA)(+) myofibroblasts, co-expressing vimentin and basement membrane proteins, but not type I collagen. TGF-beta RII(+) SMA(-) fibroblasts producing type I collagen were also increased, particularly in areas of infiltration and in ulcers. Type IV collagen and laminin were distributed throughout the gut lamina propria in disease but were restricted to the basement membrane in controls. In areas of severe epithelial damage, type IV collagen was lost and increased type I collagen was observed. To examine ECM production by these cells, mucosal mesenchymal cells were isolated. Cultured cells exhibited a similar phenotype and matrix profile to those of in vivo cells. The data suggested that there were at least two populations of mesenchymal cells responsible for ECM synthesis in the mucosa and that ligation of TGF-beta receptors on these cells resulted in the disordered and increased ECM production observed in colitic mucosa.
Whiting
Christine V
CV
Division of Veterinary Pathology, Infection and Immunity, Department of Clinical Veterinary Science, University of Bristol, Bristol, United Kingdom. c.v.whiting@bris.ac.uk
Tarlton
John F
JF
Bailey
Michael
M
Morgan
Clare L
CL
Bland
Paul W
PW
D030201:Activin Receptors, Type I / Q000378:metabolism*; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D048429:Cell Size; D002478:Cells, Cultured; D003092:Colitis / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000648:ultrastructure*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II