Intrauterine growth restriction induces skin inflammation, increases TSLP and impairs epidermal barrier function

Polányi, Laura; Niessen, Carien M.; Vohlen, Christina; Stinn, J.; Kretschmer, Tobias; Jentgen, Vanessa; Hirani, Dharmesh; Koningsbruggen-Rietschel, Silke van; Dötsch, Jörg; Alcázar, Miguel A. Alejandre

doi:10.1007/s00109-019-01867-w

Cited by 4 publications

(2 citation statements)

References 44 publications

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“…With inflammation occurring, CD68‐positive cells accumulate (Gucalp et al, 2017). In our study, the protein abundance of CD68 was significantly increased in jejunum and ileum of PGR piglets, which agreed with the increased skin mRNA expression of inflammatory markers and number of macrophages in PGR children (Polanyi et al, 2020). Moreover, the changes in the immunological barrier of PGR piglets were further evaluated by measuring sIgA and β‐defensins in the jejunal and ileal mucosa.…”

Section: Discussionsupporting

confidence: 90%

Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model

Tan

Wang

et al. 2020

Journal Cellular Physiology

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Individuals with postnatal growth retardation (PGR) are prone to developing chronic diseases. Abnormal development in small intestine is casually implicated in impaired growth. However, the exact mechanism is still implausible. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyze developmental changes in intestinal mucosal barrier function. Our data demonstrated that PGR piglets exhibited impaired jejunal and ileal epithelial villous morphology and permeability, accompanied by decreased cell proliferation ability and increased apoptosis rate. In addition, the expression of tight junction proteins (ZO‐1, claudin 1, and occludin) and E‐cadherin was markedly inhibited by PGR. The expression of P‐glycoprotein was significantly reduced in PGR piglets, as well as decreased activity of lysozyme. Moreover, the mRNA abundance and content of inflammatory cytokines were significantly increased in the intestinal mucosa and plasma of PGR piglets, respectively. PGR also contributed to lower level of sIgA, and higher level of CD68‐positive rate, β‐defensins, and protein expression involved p38 MAPK/NF‐κB pathway. Furthermore, PGR altered the intestinal microbial community such as decreased genus Alloprevotella and Oscillospira abundances, and led to lower microbial‐derived butyrate production, which may be potential targets for treatment. Collectively, our findings indicated that the intestinal mucosal barrier function of PGR piglets could develop the nutritional intervention strategies in prevention and treatment of the intestinal mucosal barrier dysfunction in piglets and humans.

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Section: Discussionsupporting

confidence: 90%

Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model

Tan

Wang

et al. 2020

Journal Cellular Physiology

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“…For example, reports indicate a significant reduction in anti-inflammatory cytokine values in the IUGR blood and gastrointestinal tract ( 84 ) versus normal body weight neonates. On the other hand, IUGR skin ( 85 ), spleen ( 55 ), and placenta ( 86 ) display a greater proinflammatory cytokine expression in the fetus/neonate compared to their respective normally grown group. Given its relevant role as an immune organ in the perinatal period, we decided to investigate the hepatic NF-κB transcriptomic adaptations to calorie restricted IUGR.…”

Section: Discussionmentioning

confidence: 99%

The Acute Hepatic NF-κB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice

et al. 2021

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Intrauterine growth restriction (IUGR) is a relevant predictor for higher rates of neonatal sepsis worldwide and is associated with an impaired neonatal immunity and lower immune cell counts. During the perinatal period, the liver is a key immunological organ responsible for the nuclear factor kappa B (NF-κB)-mediated innate immune response to inflammatory stimuli, but whether this role is affected by IUGR is unknown. Herein, we hypothesized that the newborn liver adapts to calorie-restriction IUGR by inducing changes in the NF-κB signaling transcriptome, leading to an attenuated acute proinflammatory response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic gene expression of key NF-κB factors in the IUGR and normally grown (NG) newborn mice. Real-time quantitative PCR (RT-qPCR) analysis revealed an upregulation of both IκB proteins genes (Nfkbia and Nfkbib) and the NF-κB subunit Nfkb1 in IUGR vs. NG. We next measured the LPS-induced hepatic expression of acute proinflammatory genes (Ccl3, Cxcl1, Il1b, Il6, and Tnf) and observed that the IUGR liver produced an attenuated acute proinflammatory cytokine gene response (Il1b and Tnf) to LPS in IUGR vs. unexposed (CTR). Consistent with these results, LPS-exposed hepatic tumor necrosis factor alpha (TNF-α) protein concentrations were lower in IUGR vs. LPS-exposed NG and did not differ from IUGR CTR. Sex differences at the transcriptome level were observed in the IUGR male vs. female. Our results demonstrate that IUGR induces key modifications in the NF-κB transcriptomic machinery in the newborn that compromised the acute proinflammatory cytokine gene and protein response to LPS. Our results bring novel insights in understanding how the IUGR newborn is immunocompromised due to fundamental changes in NF-κB key factors.

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Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention

White,

Yates

2023

Front. Physiol.

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Intrauterine growth restriction (IUGR) arises when maternal stressors coincide with peak placental development, leading to placental insufficiency. When the expanding nutrient demands of the growing fetus subsequently exceed the capacity of the stunted placenta, fetal hypoxemia and hypoglycemia result. Poor fetal nutrient status stimulates greater release of inflammatory cytokines and catecholamines, which in turn lead to thrifty growth and metabolic programming that benefits fetal survival but is maladaptive after birth. Specifically, some IUGR fetal tissues develop enriched expression of inflammatory cytokine receptors and other signaling cascade components, which increases inflammatory sensitivity even when circulating inflammatory cytokines are no longer elevated after birth. Recent evidence indicates that greater inflammatory tone contributes to deficits in skeletal muscle growth and metabolism that are characteristic of IUGR offspring. These deficits underlie the metabolic dysfunction that markedly increases risk for metabolic diseases in IUGR-born individuals. The same programming mechanisms yield reduced metabolic efficiency, poor body composition, and inferior carcass quality in IUGR-born livestock. The ω-3 polyunsaturated fatty acids (PUFA) are diet-derived nutraceuticals with anti-inflammatory effects that have been used to improve conditions of chronic systemic inflammation, including intrauterine stress. In this review, we highlight the role of sustained systemic inflammation in the development of IUGR pathologies. We then discuss the potential for ω-3 PUFA supplementation to improve inflammation-mediated growth and metabolic deficits in IUGR offspring, along with potential barriers that must be considered when developing a supplementation strategy.

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Intrauterine growth restriction induces skin inflammation, increases TSLP and impairs epidermal barrier function

Cited by 4 publications

References 44 publications

Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model

Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model

The Acute Hepatic NF-κB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice

Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention

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