Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases

Abstract

Abstract An in vivo model was used to investigate the role of cathepsins in mouse intestine after mechanical manipulation. Inspection of different intestine segments by immunofluorescence microscopy provided evidence for a local release of cathepsin B from cells of individual gut sections shortly after traumatic injury. Densitometry of immunoblots ruled out alterations in cathepsin B expression levels. Because similar results were obtained with both mouse and rat intestine trauma models, we were interested in identifying potential targets of released cathepsin B in early post-traumatic phases. Immunoblotting revealed initial declines followed by an increase in protein levels of claudin-1 and E-cadherin, indicating that tight junctions and cell-cell adhesions were only transiently compromised by surgical trauma. Apical aminopeptidase N and dipeptidyl peptidase IV were only slightly affected, whereas basolateral low-density lipoprotein receptors were strongly up-regulated in response to trauma. As potential targets of cathepsin B released from injured cells, we identified collagen IV and laminin of the basement membrane that was damaged during initial post-traumatic stages. Because increased collagen IV expression was observed in the intestine of cathepsin B-deficient animals, we propose a direct role of cathepsin B in that it contributes to acute post-traumatic extracellular matrix damage and may thereby facilitate onset of post-operative ileus.