Background & Aims:
The plasminogen (plg) system participates in tissue repair in several
organs, but its role in pancreas repair remains poorly characterized. To
better understand the role of plg in pancreas recovery following injury, we
examined the course of caerulein-induced pancreatitis in plg deficient and
Pancreatitis was induced by caerulein administration (50
μg/kg, 7 ip injections). Mice were sacrificed either at the acute
phase (7 hours after the first caerulein injection) or during recovery (at
2, 4 and 7 days). In pancreatic sections we examined: pancreatic morphology,
trypsin activation, inflammatory cell infiltration, acinar cell death, cell
proliferation, extracellular matrix (ECM) deposition, activation of stellate
cells (PSCs), and components of the plg and metalloproteinase systems.
In plg sufficient mice, pancreatic plg levels and plasmin activity
increased during the acute phase and remained elevated during recovery.
Pancreatitis resolved in plg sufficient mice within 7 days. Pancreas
recovery involved reorganization of the parenchyma structure, removal of
necrotic debris, cell proliferation, transient activation of PSCs and
moderate deposition of ECM proteins. Acute pancreatitis (7-h) was
indistinguishable between plg deficient and sufficient mice. In contrast,
pancreas recovery was impaired in plg deficient mice. Plg deficiency led to
disorganized parenchyma, extensive acinar cell loss, poor removal of
necrotic debris, reduced cell proliferation and fibrosis. Fibrosis was
characterized by deposition of collagens and fibronectin, persistent
activation of PSCs and upregulation of pancreatic TGF-β1.
Plg/plasmin deficiency leads to features similar to those found in
chronic pancreatitis such as parenchymal atrophy and fibrosis.