Erythropoietin Protects Intestinal Epithelial Barrier Function and Lowers the Incidence of Experimental Neonatal Necrotizing Enterocolitis

Shiou, Sheng‐Ru; Yu, Yueyue; Chen, Sangzi; Ciancio, Mae J.; Petrof, Elaine O.; Sun, Jun; Claud, Erika C.

doi:10.1074/jbc.m110.154625

Cited by 105 publications

(123 citation statements)

References 51 publications

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“…For JNK and p-JNK, it is known two bands will be detected: 46 and 54 kDa. All bands detected on blots were consistent with production information from the companies and other scientific reports which studied particular protein with antibodies ZO-1 (20,(51)(52)(53), E-Cadherin (20,39,52,53), Claudin-1 (20,53,54), 54), Occludin (52), Villin (45,55,56), JNK, p-JNK (40, 53, 57, 58), and ␤-actin (59). AvrA-e forward CAGGCCACAAAAGAAAAC AvrA-e reverse ATAACAGCCGCATCAAAC AvrA-r forward CCCAAGCTTATCTACCTCCCGGTGTCA AvrA-r reverse CGGGATCCTTGCGGGCGTCTATCTGT AvrA-cm forward…”

Section: Immunoblottingsupporting

confidence: 78%

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

Lin

Zhang

Xia

et al. 2016

Journal of Biological Chemistry

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Section: Immunoblottingsupporting

confidence: 78%

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

Lin

Zhang

Xia

et al. 2016

Journal of Biological Chemistry

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“…These include EGF, 76 and erythropoietin (EPO). 79 Much like the results observed in the use of probiotics in NEC, treatment with EGF and EPO normalized TJ components. Specifically, EGF treatment normalized expression of occludin and claudin-3, and EPO treatment normalized expression of ZO-1, when compared to untreated, NEC controls.…”

Section: Development Of the Intestinal Epithelial Barriermentioning

confidence: 69%

“…Later studies using the same model showed increased protein levels of claudins-1 and -3, but not occludin, 77 increased expression of occludin and claudin-8, but decreased expression of claudins-1, -14, and -15, 78 and increased claudin-3 without increased claudin-1 protein with loss of histological ZO-1 in pups with NEC compared to dam-fed controls. 79 Bergmann, et al, reported increased claudin-2 in both neonatal mice with NEC as well as in human NEC surgical samples. Changes in localization of occludin, claudins -2, -4 and -7 were also observed in animals with NEC, with these TJ components found primarily in the cytoplasm, rather than at the TJ.…”

Section: Development Of the Intestinal Epithelial Barriermentioning

confidence: 99%

The role of intestinal epithelial barrier function in the development of NEC

2015

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The intestinal epithelial barrier plays an important role in maintaining host health. Breakdown of intestinal barrier function is known to play a role in many diseases such as infectious enteritis, idiopathic inflammatory bowel disease, and neonatal inflammatory bowel diseases. Recently, increasing research has demonstrated the importance of understanding how intestinal epithelial barrier function develops in the premature neonate in order to develop strategies to promote its maturation. Optimizing intestinal barrier function is thought to be key to preventing neonatal inflammatory bowel diseases such as necrotizing enterocolitis. In this review, we will first summarize the key components of the intestinal epithelial barrier, what is known about its development, and how this may explain NEC pathogenesis. Finally, we will review what therapeutic strategies may be used to promote optimal development of neonatal intestinal barrier function in order to reduce the incidence and severity of NEC.

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“…In the current study, low‐dose rhEPO (500U/kg) treatment decreased the risk of NEC and sepsis and did not increase the risk of ROP or BPD. The mechanisms behind the reduced incidence of NEC and sepsis are not fully understood; however, rhEPO protects epithelial barrier function and protects intestine from excessive autophagy and apoptosis, and this, as well as rhEPO's immunomodulation actions, might provide beneficial effects in preventing NEC and sepsis 49, 50. Furthermore, there were no adverse effects such as thrombosis, hypertension, polycythemia, or polyplastocytosis observed, which is in line with previous reports,20, 37 suggesting that the current protocol of repeated low‐dose rhEPO treatment in this study is protective and safe.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Shi

Sun

et al. 2016

Annals of Neurology

115

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ObjectiveTo evaluate the efficacy and safety of repeated low‐dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants.MethodsA total of 800 infants of ≤32‐week gestational age who had been in an intensive care unit within 72 hours after birth were included in the trial between January 2009 and June 2013. Preterm infants were randomly assigned to receive rhEPO (500IU/kg; n = 366) or placebo (n = 377) intravenously within 72 hours after birth and then once every other day for 2 weeks. The primary outcome was death or moderate to severe neurological disability assessed at 18 months of corrected age.ResultsDeath and moderate/severe neurological disability occurred in 91 of 338 very preterm infants (26.9%) in the placebo group and in 43 of 330 very preterm infants (13.0%) in the rhEPO treatment group (relative risk [RR] = 0.40, 95% confidence interval [CI] = 0.27–0.59, p < 0.001) at 18 months of corrected age. The rate of moderate/severe neurological disability in the rhEPO group (22 of 309, 7.1%) was significantly lower compared to the placebo group (57 of 304, 18.8%; RR = 0.32, 95% CI = 0.19–0.55, p < 0.001), and no excess adverse events were observed.InterpretationRepeated low‐dose rhEPO treatment reduced the risk of long‐term neurological disability in very preterm infants with no obvious adverse effects. Ann Neurol 2016;80:24–34

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Erythropoietin Protects Intestinal Epithelial Barrier Function and Lowers the Incidence of Experimental Neonatal Necrotizing Enterocolitis

Cited by 105 publications

References 51 publications

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

The role of intestinal epithelial barrier function in the development of NEC

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

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