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Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model.

ABSTRACT: Necrotizing enterocolitis (NEC) is a common devastating gastrointestinal disease in premature infants, the molecular mechanisms of which have not been fully elucidated. Recently, endogenous peptides have garnered much attention owing to their role in diagnosis and treatment. However, changes in the peptide expression of NEC intestinal tissues remain poorly understood. In the present study, a comparative peptidomics profiling analysis was performed between NEC and control intestinal tissues via liquid chromatography-tandem mass spectrometry (LC-MS). In total, 103 upregulated and 73 downregulated peptides were identified in the intestinal tissues (fold?change ? 1.5, p < 0.05). Bioinformatics analysis revealed that these differentially expressed peptides were significantly associated with NEC pathophysiology, including apoptosis, the TGF-? signaling pathway, the Wnt signaling pathway, and the MAPK signaling pathway. Furthermore, two putative peptides could inhibit apoptosis and promote the migration of intestinal epithelial cells induced by lipopolysaccharide; these peptides were derived from the protein domains MT1 and EZRI, respectively. In conclusion, our study revealed that endogenous peptides are involved in the pathophysiologic mechanism of NEC; nevertheless, further exploration is required in this regard.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7790586 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model.

Liu Yiwen Y Wang Changlin C Yu Renqiang R Fan Jianfeng J Jin Weilai W Zhu Yuting Y Shi Yingzuo Y Jing Yulei Y Wang Xiaolei X Li Zhengying Z Zhou Jian J Zhang Le L

BioMed research international 20201231

Necrotizing enterocolitis (NEC) is a common devastating gastrointestinal disease in premature infants, the molecular mechanisms of which have not been fully elucidated. Recently, endogenous peptides have garnered much attention owing to their role in diagnosis and treatment. However, changes in the peptide expression of NEC intestinal tissues remain poorly understood. In the present study, a comparative peptidomics profiling analysis was performed between NEC and control intestinal tissues via l ...[more]

PMID: 33490244

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Project description:Inflammation in the premature intestine is a key factor that leads to the development of necrotizing enterocolitis (NEC). Activation of nuclear factor kappa B (NF-?B) and subsequent inflammation increases the severity of NEC. The aim of this study was to investigate the early temporal expression of inflammatory markers and activation of NF-?B in a neonatal rat model of NEC.Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed at birth, 1.5, 4, 8, and 24 hours after receiving their first feed. Control pups were vaginally delivered and mother fed; NEC was induced by a combination of gavage feeding formula, hypoxia, and enteral lipopolysaccharide (LPS); and formula fed pups were fed every 4 hours with infant formula. Ileal tissue was collected for immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. Serum was collected for cytokine content. Fold change of expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-1?, IL-6, tumor necrosis factor-? (TNF-?), IL-10, NF-?B p65, and I?B? used RT-PCR. Data were analyzed by paired two-tailed t test, expressed as mean ± standard error of the mean, and p ? 0.05 considered significant.No histologic injury was evident in ileal sections. At 1.5 h, iNOS expression increased twofold over control in NEC pups (2.1 vs. 1.0, p ? 0.05) and remained elevated at 24 h (0.7 vs. 9.4, p ? 0.05). IL-1? and IL-6 reached a peak at 24 h in NEC tissue compared with control. IL-10 expression rose in NEC pups after 4 h of insult and remained elevated in formula and NEC stressed pups. Coincident with an increase in p65 translocation into the nucleus and a reduction of I?B? detected in the cytoplasm, increased transcription of I?B? occurs.These findings suggest that NF-?B activation initiates inflammation early in the course of NEC resulting in increased proinflammatory protein expression, underscoring the importance of the inflammatory response in this NEC model, which precedes evidence of histological injury.

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Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model.

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Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model.

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