ArticleCellular and molecular gastroenterology and hepatology2022
SIGIRR Mutation in Human Necrotizing Enterocolitis (NEC) Disrupts STAT3-Dependent microRNA Expression in Neonatal Gut.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Recurrent urinary tract infection genetic risk: a systematic review and gene network analysis.International urogynecology journal · 2024Pooled it
- Necrotizing enterocolitis.Nature reviews. Disease primers · 2026Review
- Temporal mapping of epithelial vs. immune cell inflammatory shifts in the neonatal intestinal mucosa.Pediatric research · 2026Article
- Pathogenesis of necrotizing enterocolitis: mechanisms and mediators.World journal of pediatric surgery · 2026Review
- Optimising the induction of inflammation within preterm infant-derived intestinal epithelial organoids.Npj gut and liver · 2026Article
- Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives.Gut microbes · 2025Review
- Global research trends in non-coding RNA and intestinal epithelial homeostasis: an integrated bibliometric analysis (2007-2024).Hereditas · 2025Article
- Bedside Utilization of Intestinal Pathology in Preterm Infants with Surgical Necrotizing Enterocolitis.American journal of perinatology · 2025Review
- Dysbiotic Microbiota in Necrotizing Enterocolitis: Insights into Pathogenesis, Treatment, and Prevention.Gastroenterology clinics of North America · 2025Review
- Gut microbiome and inflammation in response to increasing intermittent hypoxia in the neonatal rat.Pediatric research · 2025Article
- Article
- Guardian of the gut: butyrate-regulated FUT2 protects against experimental NEC.Pediatric research · 2025Article
- The clinical characteristics and risk factors analysis within one week before the onset of necrotizing enterocolitis.Scientific reports · 2024Article
- Chromatin as alarmins in necrotizing enterocolitis.Frontiers in immunology · 2024Review
- Potential targets and mechanisms of photobiomodulation for spinal cord injury.Neural regeneration research · 2023Article
- New insights into the pathogenesis of necrotizing enterocolitis and the dawn of potential therapeutics.Seminars in pediatric surgery · 2023Review
- Necrotizing enterocolitis in premature infants-A defect in the brakes? Evidence from clinical and animal studies.Mucosal immunology · 2023Review
- The Role of the Interleukin-1 Family in Complications of Prematurity.International journal of molecular sciences · 2023Review
- Biomarkers of necrotizing enterocolitis in the era of machine learning and omics.Seminars in perinatology · 2023Review
- Short-chain fatty acids ameliorate necrotizing enterocolitis-like intestinal injury through enhancing Notch1-mediated single immunoglobulin interleukin-1-related receptor, toll-interacting protein, and A20 induction.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsSingle immunoglobulin interleukin-1-related receptor (SIGIRR) is a major inhibitor of Toll-like receptor signaling. Our laboratory identified a novel SIGIRR stop mutation (p.Y168X) in an infant who died of severe necrotizing enterocolitis (NEC). Herein, we investigated the mechanisms by which SIGIRR mutations induce Toll-like receptor hyper-responsiveness in the neonatal gut, disrupting postnatal intestinal adaptation.
methodsClustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was used to generate transgenic mice encoding the SIGIRR p.Y168X mutation. Ileal lysates, mouse intestinal epithelial cell (IEC) lysates, and intestinal sections were used to assess inflammation, signal transducer and activator of transcription 3 (STAT3) phosphorylation, microRNA (miRNA), and interleukin-1-related-associated kinase 1 (IRAK1) expression. Western blot, quantitative reverse-transcription polymerase chain reaction(qRT-PCR), and luciferase assays were performed to investigate SIGIRR-STAT3 signaling in human intestinal epithelial cells (HIEC) expressing wild-type or SIGIRR (p.Y168X) plasmids.
resultsSigirr
conclusionsOur results uncover a novel pathway (SIGIRR-STAT3-miRNA-IRAK1 repression) by which SIGIRR regulates postnatal intestine adaptation, which is disrupted by a SIGIRR mutation identified in human NEC. These data provide new insights into how human genetic mutations in SIGIRR identified in NEC result in loss of postnatal intestinal immune tolerance.
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