Cysteine cathepsins are expressed in most tissues, including the gastrointestinal tract. We demonstrated an involvement of mouse intestinal
cathepsin B in extracellular matrix remodeling for regeneration from
trauma. The present study aimed at elucidating roles of
cysteine cathepsins in the non-traumatized gastrointestinal tract of mice. Thus we investigated expression and localization patterns of
cathepsin B and its closest relative,
cathepsin X, along the length of the gastrointestinal tract, and determined the effects of their absence.
Cathepsin B showed the highest
protein levels in the anterior segments of the gastrointestinal tract, whereas the highest activity was observed in the jejunum, as revealed by
cathepsin B-specific activity-based probe labeling.
Cathepsin X was most abundant in the jejunum and
protein levels were elevated in duodenum and colon of Ctsb-/- mice. The segmental pattern of
cathepsin expression was reflected by a compartmentalized distribution of junction
proteins and basal lamina constituents, changes in tissue architecture and altered activities of the brush border
enzyme aminopeptidase N. In conclusion, we observed different compensatory effects and activity levels of
cysteine peptidases along the length of the small and large intestines in a segment-specific manner suggesting specific in situ functions of these
enzymes in particular parts of the gastrointestinal tract.