K. Schmehl et al., Deficiency of epithelial basement membrane laminin in ulcerative colitis affected human colonic mucosa, INT J COL R, 15(1), 2000, pp. 39-48
Imbalances in epithelium-matrix interactions have been discussed as a patho
mechanism in ulcerative colitis, causing a colonic mucosal barrier dysfunct
ion. Laminin. the major noncollagenous component of the basement membrane,
plays a role in epithelial basal lamina formation and promotes differentiat
ion of human enterocytes. We therefore investigated the distribution of lam
inin in ulcerative colitis affected colonic tissues. Tissue specimens from
both affected and nonaffected colonic regions were obtained from ten patien
ts with ulcerative colitis during colonoscopies or operations. Healthy tiss
ue from five patients with colorectal cancer was used as control. After his
tological classification, the localization and distribution of the basement
membrane associated extracellular matrix proteins were determined by immun
ohistochemistry. Paraffin-embedded sections were incubated with antibodies
against laminin and type IV and V collagen. No positive immunoreactivity ag
ainst laminin was found in most of the epithelial basement membranes surrou
nding the crypts in affected colonic tissues, without involvement of the su
bendothelial structures. In contrast, a type IV and V collagen accumulation
occurred in all these tissue samples. The lack of laminin in combination w
ith an overexpression of type IV and V collagen, as reported for the first
time in this paper, leads to changes in basement membrane structure. These
findings indicate that the three-dimensional network of the colonic epithel
ial basement membrane and its function are seriously disturbed in exacerbat
ing ulcerative colitis. This provides new insights into the importance of c
ell-matrix interactions for physiological and pathological mechanisms in th
e etiology of ulcerative colitis.