Acute pancreatitis is an inflammatory reaction of the pancreas caused by the premature activation of digestive enzymes. In about 20 per cent of cases, the disease takes a severe course and is accompanied by a high mortality rate. In Germany alone, more than 1,400 people die from acute pancreatitis every year.
The pancreas produces all the important digestive enzymes required by the small intestine to break down food. Most of these digestive enzymes are released from pancreatic cells as inactive protein precursers. They are not activated until they reach the small intestine. However, in the case of pancreatitis, these digestive enzymes are activated prematurely, whilst they are still in the pancreatic cells. The deciding factor is the activation of trypsinogen, a precursor of the pancreatic enzyme, to active trypsin by another proteolytic enzyme (cathepsin B). Trypsin, in turn, is able to activate further proenzymes. These then begin to digest the cell from the inside out, causing it to become necrotic and die. To counteract this premature activation, the pancreatic cells produce an inhibitor (cathepsin B inhibitor cystatin C). This is a complex natural protective mechanism of the body.
The researchers from Greifswald conducted extensive biochemical experiments and structural biological analyses. They found that this inhibition process, i.e. the inhibition of cathepsin B through cystatin C, no longer works in persons infected with the disease. In the course of pancreatitis, cystatin C is broken down and is no longer able to inhibit cathepsin B. The decomposed cystatin C in turn creates more proteins, which further increase cathepsin B activity.
Thus, the original protective mechanism starts to work against the body, causing inflammation of the pancreas. These new findings now provide an explanation of the initial intracellular events in the course of pancreatitis.
This discovery resulting from the close interdisciplinary collaboration between the working groups from the Clinic for Internal Medicine A at University Medicine Greifswald and the Institute of Biochemistry at the University of Greifswald has contributed significantly to our understanding of pancreatitis and the underlying cellular and biochemical mechanisms. The researchers at the RTG-PRO Research Training Group will continue to work on this topic in order to gain a deeper understanding of the biochemical and medically relevant aspects of acute pancreatitis. This is an important prerequisite for finding new approaches in possible treatments.
Further information
Publication:
Modenbach, J.M., Möller, C., Asgarbeik, S., Geist, N., Rimkus, N., Dörr, M., Wolfgramm, H., Steil, L., Susemihl, A., Graf, L., Schmöker, O., Böttcher, D., Hammer, E., Glaubitz, J., Lammers, M., Delcea, M., Völker, U., Aghdassi, A.A., Lerch, M.M., Weiss, F.U., Bornscheuer, U.T., Sendler, M., Biochemical analyses of cystatin-C dimers and cathepsin-B reveals a trypsin-driven feedback mechanism in acute pancreatitis, Nature Communications (https://doi.org/10.1038/s41467-025-56875-x).
Homepage of the Research Training Group: https://www.rtg2719-pro.de/de/home
Contact at the University of Greifswald
Prof. Dr. Uwe Bornscheuer
Institute of Biochemistry
Felix-Hausdorff-Straße 4, 17489 Greifswald
Tel.: +49 3834 420 4367
uwe.bornscheueruni-greifswaldde
Contact at University Medicine Greifswald
PD Dr. Matthias Sendler
Clinic for Internal Medicine A
Fleischmannstraße 41, 17475 Greifswald
Tel: +49 3834 86 80490
matthias.sendleruni-greifswaldde