ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension.American journal of human genetics · 2018Trial
- Human milk exosomal-miR-144-5p alleviates neonatal necrotizing enterocolitis by regulating the TLR4/NF-κB pathway.Pediatric research · 2026Article
- Article
- Investigating intestinal epithelium metabolic dysfunction in celiac disease using personalized genome-scale models.BMC medicine · 2025Article
- mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.Science translational medicine · 2024Article
- Gene therapy for urea cycle defects: An update from historical perspectives to future prospects.Journal of inherited metabolic disease · 2024Review
- ASL expression in ALDH1A1Human genetics · 2021Article
- Modeling age-dependent developmental changes in the expression of genes involved in citrulline synthesis using pig enteroids.Physiological reports · 2020Article
- Saccharomyces boulardii modulates necrotizing enterocolitis in neonatal mice by regulating the sirtuin 1/NF‑κB pathway and the intestinal microbiota.Molecular medicine reports · 2020Article
- Precision-based modeling approaches for necrotizing enterocolitis.Disease models & mechanisms · 2020Review
- Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer.Cell reports · 2018Article
- [Research advances in necrotizing enterocolitis in neonates].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Review
- Expanding the phenotype in argininosuccinic aciduria: need for new therapies.Journal of inherited metabolic disease · 2017Article
- Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study.Scientific reports · 2016Article
- The immunological landscape in necrotising enterocolitis.Expert reviews in molecular medicine · 2016Review
- Smad7 interrupts TGF-β signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis.Pediatric research · 2016Article
- Arginine and citrulline and the immune response in sepsis.Nutrients · 2015Review
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Necrotizing enterocolitis (NEC), the most common neonatal gastrointestinal emergency, results in significant mortality and morbidity, yet its pathogenesis remains unclear. Argininosuccinate lyase (ASL) is the only enzyme in mammals that is capable of synthesizing arginine. Arginine has several homeostatic roles in the gut and its deficiency has been associated with NEC. Because enterocytes are the primary sites of arginine synthesis in neonatal mammals, we evaluated the consequences of disruption of arginine synthesis in the enterocytes on the pathogenesis of NEC. We devised a novel approach to study the role of enterocyte-derived ASL in NEC by generating and characterizing a mouse model with enterocyte-specific deletion of Asl (Asl(flox/flox); VillinCre(tg/+), or CKO). We hypothesized that the presence of ASL in a cell-specific manner in the enterocytes is protective in the pathogenesis of NEC. Loss of ASL in enterocytes resulted in an increased incidence of NEC that was associated with a proinflammatory state and increased enterocyte apoptosis. Knockdown of ASL in intestinal epithelial cell lines resulted in decreased migration in response to lipopolysaccharide. Our results show that enterocyte-derived ASL has a protective role in NEC.
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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.