ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Transforming growth factor-β2 is sequestered in preterm human milk by chondroitin sulfate proteoglycans.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular dynamics simulations to understand glycosaminoglycan interactions in the free- and protein-bound states.Current opinion in structural biology · 2022Review
- Computerized Molecular Modeling for Discovering Promising Glycosaminoglycan Oligosaccharides that Modulate Protein Function.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Role of macrophages in fetal development and perinatal disorders.Pediatric research · 2021Review
- Combinatorial Virtual Library Screening Study of Transforming Growth Factor-β2-Chondroitin Sulfate System.International journal of molecular sciences · 2021Article
- It's all in the milk: chondroitin sulfate as potential preventative therapy for necrotizing enterocolitis.Pediatric research · 2021Review
- Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools.Frontiers in cell and developmental biology · 2021Review
- Necrotizing Enterocolitis: LPS/TLR4-Induced Crosstalk Between Canonical TGF-β/Wnt/β-Catenin Pathways and PPARγ.Frontiers in pediatrics · 2021Review
- A Review of the Immunomodulating Components of Maternal Breast Milk and Protection Against Necrotizing Enterocolitis.Nutrients · 2019Review
- Effect of HTST and Holder Pasteurization on the Concentration of Immunoglobulins, Growth Factors, and Hormones in Donor Human Milk.Frontiers in immunology · 2018Article
- Cytokines and growth factors in the developing intestine and during necrotizing enterocolitis.Seminars in perinatology · 2017Review
- Smad7 interrupts TGF-β signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis.Pediatric research · 2016Article
- The Phylogeny, Ontogeny, and Organ-specific Differentiation of Macrophages in the Developing Intestine.Newborn (Clarksville, Md.)Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Human milk contains biologically important amounts of transforming growth factor-β2 isoform (TGF-β2), which is presumed to protect against inflammatory gut mucosal injury in the neonate. In preclinical models, enterally administered TGF-β2 can protect against experimental necrotizing enterocolitis, an inflammatory bowel necrosis of premature infants. In this study, we investigated whether TGF-β bioactivity in human preterm milk could be enhanced for therapeutic purposes by adding recombinant TGF-β2 (rTGF-β2) to milk prior to feeding. Milk-borne TGF-β bioactivity was measured by established luciferase reporter assays. Molecular interactions of TGF-β2 were investigated by nondenaturing gel electrophoresis and immunoblots, computational molecular modeling, and affinity capillary electrophoresis. Addition of rTGF-β2 (20-40 nM) to human preterm milk samples failed to increase TGF-β bioactivity in milk. Milk-borne TGF-β2 was bound to chondroitin sulfate (CS) containing proteoglycan(s) such as biglycan, which are expressed in high concentrations in milk. Chondroitinase treatment of milk increased the bioactivity of both endogenous and rTGF-β2, and consequently, enhanced the ability of preterm milk to suppress LPS-induced NF-κB activation in macrophages. These findings provide a mechanism for the normally low bioavailability of milk-borne TGF-β2 and identify chondroitinase digestion of milk as a potential therapeutic strategy to enhance the anti-inflammatory effects of preterm milk.
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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.