Epidermal Growth Factor Protects against Pancreatic Damage in Cerulein-Induced Pancreatitis

Abstract

Epidermal growth factor (EGF) exhibits gastroprotective and ulcer-healing action. These observations prompted us to determine the influence of EGF on cerulein-induced pancreatitis (CIP) in the rat. Acute pancreatitis was induced by subcutaneous infusion of cerulein (10 μg/kg/h) for 5 h. Initially EGF was administrated twice at doses of 1, 5, 10 or 100 μg/kg s.c. (first injection 30 min prior to cerulein infusion, and the second injection 2.5 h after the start of cerulein infusion) and from this part of study 10 μg/kg was chosen for the next experiments. CIP led to a significant decrease in DNA synthesis and a reduction in pancreatic blood flow (PBF) by 42 and 30%, respectively, as well as a significant increase in pancreatic weight, plasma amylase concentration, plasma interleukin-1β (IL-1β) level and the development of the histological signs of pancreatic damage with marked edema, leukocyte infiltration and vacuolization of acinar cells. Treatment with EGF attenuated the pancreatic tissue damage in CIP as manifested by partial reversal of the drop in DNA synthesis and improvement of pancreatic histology. Moreover, EGF administration attenuated the fall in PBF and significantly reduced the cerulein-evoked increase in pancreatic weight. Also plasma amylase and IL-1β were decreased in rats treated with EGF. We conclude that: (1) EGF exerts a protective effect against CIP, and (2) the beneficial activity of EGF in CIP seems to depend on the increase in pancreatic cell proliferation, the reduction in cytokine generation and the attenuation of the fall in PBF.

Reg4 protects against acinar cell necrosis in experimental pancreatitis

“…The EGFR signalling pathway plays a key role in protecting against caerulein-evoked pancreatic damage 30 31. EGF family ligands can bind to the extracellular domain of EGFR and induce phosphorylation at specific tyrosine residues within the receptor cytoplasmic domain.…”

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

“…EGFR activation by either EGF or betacellulin has been shown to protect against development of acute pancreatitis, in association with pancreatic cell proliferation, decreased inflammatory cytokine/chemokine production, and maintenance of blood flow to the pancreas (113,309,550,590). However, EGFR activation is also implicated in the development of pancreatic fibrosis resulting from chronic pancreatitis.…”

Epidermal Growth Factor Serum Levels and the 61 G/A Polymorphism in Patients with Acute Pancreatitis

“…Animal studies have shown that growth factors which include EGF, along with hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1), attenuate the pancreatic damage following an attack of AP [9,18,19]. EGF is a powerful mitogen, which modulates pancreatic secretion and stimulates pancreatic growth [20,21].…”

“…Subsequently, EGF molecules bind to such receptors on the acinar cells and promote pancreatic regeneration and recovery [8]. When administered before and during the induction of cerulein-induced pancreatitis in rats, EGF protects against pancreatic damage [9]. In acute necrotizing pancreatitis animal models, treatment with EGF prevents the development of septic complications [10].…”