{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:41:33Z","timestamp":1790361693416,"version":"4.1.0"},"reference-count":108,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oklahoma Center for Microbial Pathogenesis and Immunity","award":["5P20GM134973"],"award-info":[{"award-number":["5P20GM134973"]}]},{"name":"Oklahoma Center for Microbial Pathogenesis and Immunity","award":["R01HD109784"],"award-info":[{"award-number":["R01HD109784"]}]},{"name":"NIH NICHD","award":["5P20GM134973"],"award-info":[{"award-number":["5P20GM134973"]}]},{"name":"NIH NICHD","award":["R01HD109784"],"award-info":[{"award-number":["R01HD109784"]}]},{"name":"Children\u2019s Health Foundation","award":["5P20GM134973"],"award-info":[{"award-number":["5P20GM134973"]}]},{"name":"Children\u2019s Health Foundation","award":["R01HD109784"],"award-info":[{"award-number":["R01HD109784"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human milk (HM) is rich in bioactive factors promoting postnatal small intestinal development and maturation of the microbiome. HM is also protective against necrotizing enterocolitis (NEC), a devastating inflammatory condition predominantly affecting preterm infants. The HM glycosaminoglycan, hyaluronan (HA), is present at high levels in colostrum and early milk. Our group has demonstrated that HA with a molecular weight of 35 kDa (HA35) promotes maturation of the murine neonatal intestine and protects against two distinct models of NEC. However, the molecular mechanisms underpinning HA35-induced changes in the developing ileum are unclear. CD-1 mouse pups were treated with HA35 or vehicle control daily, from P7 to P14, and we used network and functional analyses of bulk RNA-seq ileal transcriptomes to further characterize molecular mechanisms through which HA35 likely influences intestinal maturation. HA35-treated pups separated well by principal component analysis, and cell deconvolution revealed increases in stromal, Paneth, and mature enterocyte and progenitor cells in HA35-treated pups. Gene set enrichment and pathway analyses demonstrated upregulation in key processes related to antioxidant and growth pathways, such as nuclear factor erythroid 2-related factor-mediated oxidative stress response, hypoxia inducible factor-1 alpha, mechanistic target of rapamycin, and downregulation of apoptotic signaling. Collectively, pro-growth and differentiation signals induced by HA35 may present novel mechanisms by which this HM bioactive factor may protect against NEC.<\/jats:p>","DOI":"10.3390\/ijms252312679","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:02:18Z","timestamp":1732593738000},"page":"12679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Network-Based Bioinformatics Highlights Broad Importance of Human Milk Hyaluronan"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-5383","authenticated-orcid":false,"given":"Kathryn Y.","family":"Burge","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-564X","authenticated-orcid":false,"given":"Hala","family":"Chaaban","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100127","DOI":"10.1016\/j.advnut.2023.09.015","article-title":"Human Milk Bioactive Components and Child Growth and Body Composition in the First 2 Years: A Systematic Review","volume":"15","author":"Brockway","year":"2024","journal-title":"Adv. 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