Background Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency and the leading surgical cause of death in premature infants. We have shown that administration of exogenous heparin-binding EGF-like growth factor (HB-EGF) in protects the intestines from experimental NEC. The aim of the current study was to evaluate the effect of gain-of-function of endogenous HB-EGF on susceptibility to NEC. Methods Neonatal HB-EGF transgenic (TG) mice and their wild type (WT) counterparts were exposed to experimental NEC. An additional group of HB-EGF TG pups were also exposed to NEC, but received the HB-EGF antagonist cross-reacting material 197 (CRM 197) injected subcutaneously immediately after birth. To examine gut barrier function, HB-EGF TG and WT pups received intragastric fluorescein isothiocyanate-labeled dextran (FITC-dextran) under basal and stressed conditions, and serum FITC-dextran levels were measured. Results WT mice had an incidence of NEC of 54.2% whereas HB-EGF TG mice had a significantly decreased incidence of NEC of 22.7% (p=0.03). Importantly, administration of CRM 197 to HB-EGF TG pups significantly increased the incidence of NEC to 65% (p=0.004). HB-EGF TG mice had significantly decreased intestinal permeability compared to WT mice both under basal and stressed conditions. Conclusions Our results provide evidence that over expression of the HB-EGF gene decreases susceptibility to NEC, and that administration of the HB-EGF antagonist CRM 197 reverses this protective effect.

Background We have previously demonstrated that mesenchymal stem cell (MSC) administration protects the intestines from injury in a mouse model of intestinal ischemia/reperfusion (I/R) injury. We have also shown that heparin-binding EGF-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent in vivo that may protect the intestines via its effects on SC (SC). The goal of the current study was to examine the effects of HB-EGF on both amniotic fluid (AF)- and bone marrow (BM)-derived MSCs in vitro. Materials and Methods MSCs were isolated from the amniotic fluid and bone marrow of pan-EGFP mice, grown in MSC-specific culture medium, and purified by sequential passages based on their adherence properties. Pluripotency was confirmed by induced differentiation. After incubation of MSCs with HB-EGF, proliferation was quantified using the CyQuant cell proliferation assay kit under normoxic and anoxic conditions, chemotaxis was quantified using the CHEMICON QCM cell migration kit, and apoptosis was determined by caspase-3 immunohistochemistry after exposure of MSC to anoxic stress. Results AF-MSC and BM-MSC showed significantly increased proliferation and migration in response to HB-EGF. HB-EGF significantly protected AF-MSC and BM-MSC from anoxia-induced apoptosis. The proliferative and anti-apoptotic effects of HB-EGF were even more pronounced in AF-MSC compared with BM-MSC. Conclusions These results demonstrate that HB-EGF acts as a mitogenic and chemotactic agent for MSC that protects MSC from injury. These findings may have important implications for future experiments designed to utilize MSC to protect the intestines from injury.

Background-The aim of the current study was to determine whether overexpression of HB-EGF could protect the intestines from injury after hemorrhagic shock and resuscitation (HS/R) in mice.

Purpose Radiation therapy (RT) often induces enteritis by inhibiting proliferation and inducing apoptosis. Heparin-binding EGF-like growth factor (HB-EGF) has been shown to protect the intestine in several animal injury models. The objective of this study was to examine whether HB-EGF affects RT-induced intestinal injury. Methods HB-EGF or PBS was administered intraperitoneally to mice daily for 3 days, followed by total body irradiation (TBI). Three days after TBI, intestinal segments were harvested, and BrdU immunohistochemistry was performed to identify proliferating crypts (n=25). Four days after TBI, intestinal segments were harvested and assessed for histologic injury (n=34), and FITC-dextran was administered via gavage with serum FITC-dextran levels quantified to determine gut barrier function (n=18). Results Compared to non-HB-EGF-treated irradiated mice, administration of HB-EGF to irradiated mice led to a significantly increased percentage of proliferative crypts (72.6% vs. 50.5%, p=0.001), a significantly decreased percent of histologic sections with severe histologic injury (13.7% vs. 20.3%, p=0.005), and significantly reduced intestinal permeability (18.8 µg/mL vs. 22.6 µg/mL, p=0.02). Conclusions These results suggest that administration of HB-EGF protects the intestines from injury after exposure to radiation therapy. Administration of HB-EGF may represent a novel therapy for the prevention of radiation enteritis in the future.

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Excessive sound, vibration, and light are detrimental to rodent welfare, yet these parameters are rarely recorded in vivaria. Whether housing environments exceed the suggested thresholds and which specific factors may alter these parameters is generally unknown. The goal of this study was to determine how environmental factors may alter sound, vibration, and light at the room and cage levels. Measurements were made using an ultrasonic microphone, accelerometer, and light sensor. Measurement sites were 1) in open air at a central location in 64 rooms located in 9 buildings, and 2) inside an empty mouse or rat cage containing chow, water, and bedding and located on an animal transfer station (n = 51) or housing rack (n = 102). Information collected for each transfer station and rack measurement included the year of manufacture, the species on the rack, and the number of cages on the rack. For each location, a baseline measurement was taken with the transfer station turned off, followed by another measurement after the transfer station was turned on. In general, many factors influenced ambient sound, vibration, and light, indicating that values are not uniform across rodent rooms in the same institution or across cages in a single room. Sound peaks capable of startling rodents were measured in association with hallway ultrasonic motion sensors and during cage change. Vibration and light intensity were generally low when cages were located on the rack. In contrast, active transfer stations had more vibration and light intensity, reaching levels that were potentially stressful for rodents. These data reflect the ambient sound, vibration, and light that rodents experience during normal facility operations. These patterns may extend to other locations, but given the variability in all parameters, the data highlight the need for institutions to conduct their own monitoring.

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