Motherʼs Milk-Induced Hsp70 Expression Preserves Intestinal Epithelial Barrier Function in an Immature Rat Pup Model

Abstract

Preterm infants face many challenges in transitioning from the in utero to extrauterine environment while still immature. Failure of the preterm gut to successfully mature to accommodate bacteria and food substrate leads to significant morbidity such as neonatal necrotizing enterocolitis. The intestinal epithelial barrier plays a critical role in gut protection. Heat shock protein 70 (Hsp70) is an inducible cytoprotective molecule shown to protect the intestinal epithelium in adult models. To investigate the hypothesis that Hsp70 may be important for early protection of the immature intestine, Hsp70 expression was evaluated in intestine of immature rat pups. Data demonstrate that Hsp70 is induced by exposure to mother’s milk. Hsp70 is found in mother’s milk, and increased Hsp70 transcription is induced by mother’s milk. This Hsp70 colocalizes with the tight junction protein ZO-1. Mother’s milk-induced Hsp70 may contribute to maintenance of barrier function in the face of oxidant stress. Further understanding of the means by which mother’s milk increases Hsp70 in the ileum will allow potential means of strengthening the intestinal barrier in at-risk preterm infants.

Preinduction of heat shock protein 70 protects mice against post-infection irritable bowel syndrome via NF-κB and NOS/NO signaling pathways

“…In the current study, Trichinella spiralis infection reduced ileal ZO1 and occludin1 abundances, which may contribute to the alteration in intestinal permeability. Liedel et al reported that mother's milk-induced HSP70 expression preserves intestinal epithelial barrier function in an immature rat pup model (Liedel et al 2011), which is similar with our results that preinduction of HSP70 significantly reversed the intestinal dysfunction caused by Trichinella spiralis infection. There are also a large number of studies demonstrating a protective role of HSP70 in intestinal barrier, including ischemiareperfusion (I/R) mucosal injury (Fleming et al 2002), ethanol-induced intestinal damage (Lee et al 2014a), and chronic water avoid stress (Yang et al 2009).…”

Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota

“…54 Conversely, decreased intestinal HSP70 and leaky intestine were reported in a model of necrotic enterocolitis in rats. 55 In summary, iHSPs have many vital cellular functions. Expression of iHSPs is modulated by inflammatory and oxidative stress and is involved in major cellular physiological functions of GECs.…”

“…89 In a rat model of necrotizing enterocolitis induced by maternal separation and milk formula feeding, the expression of both ileal iHSP70 protein and gene was reduced. 55 Mother's milk was hypothesized to induce physiological levels of iHSP70 in normal rat pups, though precise mechanisms were not disclosed. 55 Another group confirmed reduced intestinal iHSP70 in both human and mouse necrotizing enterocolitis.…”

“…55 Mother's milk was hypothesized to induce physiological levels of iHSP70 in normal rat pups, though precise mechanisms were not disclosed. 55 Another group confirmed reduced intestinal iHSP70 in both human and mouse necrotizing enterocolitis. 90 Of note, heat preconditioning of rat pups increased ileal iHSP, inhibited NF-jB activation, and reduced necrotizing enterocolitis-induced tissue alterations.…”

“…Rat milk may be responsible for the induction of intestinal iHSP70 in rat pup, though mechanisms were not disclosed. 55 Wu et al 13 suggested that milk L-glutamine could be responsible for this effect. Conversely, a peptide mixture (n ¼ 25 peptides; molecular weight, 1-5 kDa) from buffalo cheese acid whey was reported to decrease iHSP70 concentrations in Caco2 cells, making them more sensitive to oxidative stress.…”