ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Smad7 inhibits autocrine expression of TGF-β2 in intestinal epithelial cells in baboon necrotizing enterocolitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 64 citations in OpenAlex.
- Trial
- TGF-β2, a protective intestinal cytokine, is abundant in maternal human milk and human-derived fortifiers but not in donor human milk.Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine · 2013Trial
- Ice Templated PEG-Alginate Double-Network Cryogels with Tunable Mechanics and Degradation for Soft Tissue Engineering.Gels (Basel, Switzerland) · 2026Article
- Microtubular Disruption Alters Intestinal Permeability in Murine Neonatal Anemic Intestine.Anemia · 2026Article
- The microbiome's hidden influence: preclinical insights into inflammatory responses in necrotizing enterocolitis.Seminars in immunopathology · 2025Review
- Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.Biomedicines · 2025Review
- 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
- 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
- Review
- Stem cell derived therapies to preserve and repair the developing intestine.Seminars in perinatology · 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
- State-of-the-art review and update ofFrontiers in pediatrics · 2023Review
- Gut-Brain cross talk: The pathogenesis of neurodevelopmental impairment in necrotizing enterocolitis.Frontiers in pediatrics · 2023Review
- Role of macrophages in fetal development and perinatal disorders.Pediatric research · 2021Review
- The role of TGF-β2 in cartilage development and diseases.Bone & joint research · 2021Article
- Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer.International journal of molecular sciences · 2021Review
- Necrotizing Enterocolitis: LPS/TLR4-Induced Crosstalk Between Canonical TGF-β/Wnt/β-Catenin Pathways and PPARγ.Frontiers in pediatrics · 2021Review
- Cytokine Expression by Human Macrophage-Like Cells Derived from the Monocytic Cell Line THP-1 Differs Between Treatment With Milk from Preterm- and Term-Delivering Mothers and Pasteurized Donor Milk.Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Preterm infants may be at risk of necrotizing enterocolitis (NEC) due to deficiency of transforming growth factor-β 2 (TGF-β(2)) in the developing intestine. We hypothesized that low epithelial TGF-β(2) expression in preterm intestine and during NEC results from diminished autocrine induction of TGF-β(2) in these cells. Premature baboons delivered at 67% gestation were treated per current norms for human preterm infants. NEC was diagnosed by clinical and radiological findings. Inflammatory cytokines, TGF-β(2), Smad7, Ski, and strawberry notch N (SnoN)/Ski-like oncoprotein (SKIL) was measured using quantitative reverse transcriptase-polymerase chain reaction, immunoblots, and immunohistochemistry. Smad7 effects were examined in transfected IEC6 intestinal epithelial cells in vitro. Findings were validated in archived human tissue samples of NEC. NEC was recorded in seven premature baboons. Consistent with existing human data, premature baboon intestine expressed less TGF-β(2) than term intestine. TGF-β(2) expression was regulated in epithelial cells in an autocrine fashion, which was interrupted in the premature intestine and during NEC due to increased expression of Smad7. LPS increased Smad7 binding to the TGF-β(2) promoter and was associated with dimethylation of the lysine H3K9, a marker of transcriptional silencing, on the nucleosome of TGF-β(2). Increased Smad7 expression in preterm intestine was correlated with the deficiency of SnoN/SKIL, a repressor of the Smad7 promoter. Smad7 inhibits autocrine expression of TGF-β(2) in intestinal epithelial cells in the normal premature intestine and during NEC. Increased Smad7 expression in the developing intestine may be due to a developmental deficiency of the SnoN/SKIL oncoprotein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.