Hyaluronan 35 kDa enhances epithelial barrier function and protects against the development of murine necrotizing enterocolitis

Abstract

Background-Disruption of tight junctions (TJ) predisposes to bacterial translocation, intestinal inflammation, and necrotizing enterocolitis (NEC). Previously studies showed that hyaluronan (HA), a glycosaminoglycan in human milk, maintains intestinal permeability, enhances intestinal immunity, and reduces intestinal infections. In this study, we investigated the effects of HA 35 kDa, on a NEC-like murine model. Methods-Pups were divided into Sham, NEC, NEC + HA 35, and HA 35. Severity of intestinal injury was compared using a modified macroscopic gut scoring and histologic injury grading. The effect of HA 35 on intestinal permeability was determined by measuring FITC dextran and bacterial translocation. RNA and protein expression of TJ proteins (claudin 2, 3, 4, occludin, and ZO-1) were compared between the groups.Results-Pups in the NEC + HA 35 group had increased survival and lower intestinal injury compared to untreated NEC. In addition, HA 35 reduced intestinal permeability, bacterial translocation, and proinflammatory cytokine release. Ileal expression of claudins 2, 3, 4, occludin and ZO-1 was upregulated in NEC + HA 35 and HA 35 compared to untreated NEC and shams.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

The Role of Glycosaminoglycans in Protection from Neonatal Necrotizing Enterocolitis: A Narrative Review

“…Hill et al [173] demonstrated a polydisperse HM HA extract is capable of protecting colonocytes from Salmonella infection in vitro. Mice treated with HA 35 are protected from Citrobacter rodentium infection via an upregulation in the critical tight junction protein, ZO-1 (zonula occludens-1), resulting in reduced intestinal permeability and inhibited bacterial translocation across colonic epithelium [193], similar to our findings in a murine NEC model [179].…”

“…Our group recently demonstrated the effectiveness of HA 35 in reducing the incidence and severity of disease in a mouse model of necrotizing enterocolitis. Gunasekaran et al [179] treated mouse pups (age P14-16) with HA 35 (15 mg/kg or 30 mg/kg) once per day for three days prior to the initiation of NEC. NEC was induced using a two-hit model of intraperitoneal dithizone injection followed by oral administration of Klebsiella pneumoniae [55].…”

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

“…With these abundant issues associated with NEC, it is incumbent upon researchers to develop targeted, specific treatments for the disease. BM components, such as human milk saccharides (i.e., oligosaccharides like 2'-fucosyllactose and glycosaminoglycans like hyaluronan) and anti-microbial peptides (i.e., lactoferrin), have proven to have some efficacy in the treatment of NEC [93,112,113].…”

The Role of Hyaluronan Treatment in Intestinal Innate Host Defense

“…The first one occurs at the local cellular level. HA binds to specific cell surface receptors such as CD44, (9,10) Undefined Topical Treatment for interstitial cystitis/painful bladder syndrome (11) HA 750 kDa IP Proliferation of colonic epithelium in vivo (12) HA 750 kDa IP Protection from DSS-induced colitis in vitro and in vivo (13) HA 750 kDa IP Protection from irradiation in vivo (14) HA (20) HA molecular mass and route of administration appear to be important for specific efficacy.…”