HB-EGF Protects the Lungs after Intestinal Ischemia/Reperfusion Injury

Abstract

Background Acute respiratory distress syndrome continues to be a major source of morbidity and mortality in critically-ill patients. Heparin binding EGF-like growth factor (HB-EGF) is a biologically active protein that acts as an intestinal cytoprotective agent. We have previously demonstrated that HB-EGF protects the intestines from injury in several different animal models of intestinal injury. In the current study, we investigated the ability of HB-EGF to protect the lungs from remote organ injury after intestinal ischemia/reperfusion (I/R). Methods Mice were randomly assigned to one of the following groups: 1) sham-operated; 2) sham + HB-EGF (1200 µg/kg in 0.6 mL administered by intra-luminal injection at the jejuno-ileal junction immediately after identification of the superior mesenteric artery); 3) superior mesenteric artery occlusion for 45 min followed by reperfusion for 6 h (I/R); or 4) I/R+HB-EGF (1200 µg/kg in 0.6 mL) administered 15 min after vascular occlusion. The severity of acute lung injury was determined by histology, morphometric analysis and invasive pulmonary function testing. Animal survival was evaluated using Kaplan-Meier analysis. Results Mice subjected to intestinal I/R injury showed histological and functional evidence of acute lung injury and decreased survival compared to sham-operated animals. Compared to mice treated with HB-EGF (I/R + HB-EGF), the I/R group had more severe acute lung injury, and decreased survival. Conclusion Our results demonstrate that HB-EGF reduces the severity of acute lung injury after intestinal I/R in mice. These data demonstrate that HB-EGF may be a potential novel systemic anti-inflammatory agent for the prevention of the systemic inflammatory response syndrome (SIRS) after intestinal injury.

TLR4 Mediates Lung Injury and Inflammation in Intestinal Ischemia-Reperfusion

“…Our findings implicated a critical role of TLR4 signaling in lung inflammatory injury triggered by intestinal I/R. Secondary lung inflammatory response plays a key role in the pathogenesis of acute lung injury in gut I/R [13][14][15], but the mechanisms of this process are poorly understood. Accumulation of neutrophils in the lung is a prominent feature of ALI after intestinal I/R [16].…”

Heparin-binding EGF-like growth factor (HB-EGF) therapy for intestinal injury: Application and future prospects

“…Using the model of I/R, we investigated the ability of HB-EGF to protect the lungs from remote organ injury after intestinal I/R. We found that administration of HB-EGF led to decreased congestion of septae, reduced intra-alveolar inflammatory cell infiltration, decreased hemorrhage, and decreased cellular apoptosis in the lungs [93]. These results demonstrate that HB-EGF reduces the severity of acute lung injury after intestinal I/R in mice, and that HB-EGF may be a potential novel systemic anti-inflammatory agent for the prevention of distant organ associated with SIRS after intestinal injury.…”

Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury

“…1F). Because growth factor pathways have been implicated in various organs in response to IR injury (Casillas-Ramirez et al 2009, James et al 2010, Brzozowski et al 2012, we then evaluated the effect of IR on endogenous EGF and its receptor expression in testis. The plasma EGF remained relatively high along the study period but unexpectedly, no statistical difference was detected (Fig.…”