Prenatal inflammation impairs intestinal microvascular development through a TNF-dependent mechanism and predisposes newborn mice to necrotizing en…

A new interesting article has been published in Am J Physiol Gastrointest Liver Physiol. 2019 May 24. doi: 10.1152/ajpgi.00332.2018. and titled:

Prenatal inflammation impairs intestinal microvascular development through a TNF-dependent mechanism and predisposes newborn mice to necrotizing en…

Authors of this article are:

Yan X, Managlia E, Tan XD, De Plaen IG.

A summary of the article is shown below:

Prenatal inflammation is a risk factor for necrotizing enterocolitis (NEC) and it increases intestinal injury in a rat NEC model. We previously showed that maldevelopment of the intestinal microvasculature and lack of VEGFR2 signaling play a role in experimental NEC. However, whether prenatal inflammation affects the intestinal microvasculature remains unknown. In this study, mouse dams were injected intraperitoneally with lipopolysaccharide (LPS) or saline at E17. Neonatal intestinal microvasculature density, endothelial cell proliferation and intestinal VEGF-A (VEGF) and VEGFR2 proteins were assessed in vivo. Maternal and fetal serum TNF concentrations were measured by ELISA. The impact of TNF on the neonatal intestinal microvasculature was examined in vitro and in vivo, and we determined whether prenatal LPS injection worsened experimental NEC via TNF. Here we found that prenatal LPS injection significantly decreased intestinal microvascular density, endothelial cell proliferation and VEGF and VEGFR2 protein expression in neonatal mice. Prenatal LPS injection increased maternal and fetal serum level of TNF. TNF decreased VEGFR2 protein in vitro in neonatal endothelial cells. Postnatal TNF administration in vivo decreased microvasulature density, endothelial cell proliferation and VEGF and VEGFR2 protein, and increased the incidence of severe NEC, and these effects were ameliorated by stabilizing HIF-1a, the master regulator of VEGF. Furthermore, prenatal LPS injection significantly increased the incidence of severe NEC in our model, and the effect was dependent on endogenous TNF. Our study suggests that prenatal inflammation increases the susceptibility to NEC, downregulates intestinal VEGFR2 signaling and affects perinatal intestinal microvascular development via a TNF mechanism.

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This article is a good source of information and a good way to become familiar with topics such as: endothelial cells; inflammation; intestinal microvasculature; necrotizing enterocolitis; neonate.