ArticlePediatric research2016
Smad7 interrupts TGF-β signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis.
Article in Pediatric research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Trial
- Evolving role of mitochondrial dysfunction and mitophagy in necrotizing enterocolitis.Pediatric research · 2026Article
- Microtubular Disruption Alters Intestinal Permeability in Murine Neonatal Anemic Intestine.Anemia · 2026Article
- Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives.Gut microbes · 2025Review
- Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.Biomedicines · 2025Review
- Bedside Utilization of Intestinal Pathology in Preterm Infants with Surgical Necrotizing Enterocolitis.American journal of perinatology · 2025Review
- Lipopolysaccharide-Activated Macrophages Suppress Cellular Senescence and Promote Rejuvenation in Human Dermal Fibroblasts.International journal of molecular sciences · 2025Article
- Platelet specific knockout of integrin beta-3 (β3) reduces severity of necrotizing enterocolitis in murine neonates.Frontiers in pediatrics · 2025Article
- Stored RBC transfusions leads to the systemic inflammatory response syndrome in anemic murine neonates.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Assessment of inflammatory biomarkers to identify surgical/death necrotizing enterocolitis in preterm infants without pneumoperitoneum.Pediatric surgery international · 2024Article
- Extracellular Nicotinamide Phosphoribosyltransferase Is a Therapeutic Target in Experimental Necrotizing Enterocolitis.Biomedicines · 2024Article
- Immunological aspects of necrotizing enterocolitis models: a review.Frontiers in immunology · 2024Review
- Super Carbonate Apatite-miR-497a-5p Complex Is a Promising Therapeutic Option against Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Clinical determinants and impact of hemorrhagic lesions on intestinal pathology in preterm infants with surgical necrotizing enterocolitis.Journal of neonatal-perinatal medicine · 2023Article
- Smad7 as a positive regulator of intestinal inflammatory diseases.Current research in immunology · 2023Review
- New insights into intestinal macrophages in necrotizing enterocolitis: the multi-functional role and promising therapeutic application.Frontiers in immunology · 2023Review
- Recent advances in our understanding of NEC diagnosis, prognosis and surgical approach.Frontiers in pediatrics · 2023Review
- Clinical and histopathological correlates of intestinal repair in preterm infants following surgical necrotizing enterocolitis.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2022Article
- Bench to bedside - new insights into the pathogenesis of necrotizing enterocolitis.Nature reviews. Gastroenterology & hepatology · 2022Review
- Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells.Journal of translational medicine · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNecrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. Based on our recent findings of increased Smad7 expression in surgically resected bowel affected by NEC, we hypothesized that NEC macrophages undergo inflammatory activation because increased Smad7 expression renders these cells resistant to normal, gut-specific, transforming growth factor (TGF)-β-mediated suppression of inflammatory pathways.
methodsWe used surgically resected human NEC tissue, murine models of NEC-like injury, bone marrow-derived and intestinal macrophages, and RAW264.7 cells. Smad7 and IκB kinase-beta (IKK-β) were measured by quantitative PCR, western blots, and immunohistochemistry. Promoter activation was confirmed in luciferase reporter and chromatin immunoprecipitation assays.
resultsNEC macrophages showed increased Smad7 expression, particularly in areas with severe tissue damage and high bacterial load. Lipopolysaccharide-induced Smad7 expression suppressed TGF-β signaling and augmented nuclear factor-kappa B (NF-κB) activation and cytokine production in macrophages. Smad7-mediated NF-κB activation was likely mediated via increased expression of IKK-β, which, further increased Smad7 expression in a feed-forward loop. We show that Smad7 induced IKK-β expression through direct binding to the IKK-β promoter and its transcriptional activation.
conclusionSmad7 expression in NEC macrophages interrupts TGF-β signaling and promotes NF-κB-mediated inflammatory signaling in these cells through increased expression of IKK-β.
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