Amniotic fluid-borne hepatocyte growth factor protects rat pups against experimental necrotizing enterocolitis

Sunil Jain, Eric W. Baggerman, Krishnan MohanKumar, Kopperuncholan Namachivayam, Ramasamy Jagadeeswaran, Victor Reyes, Akhil Maheshwari

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to amniotic fluid-borne growth factors, possibly contributing to the increased risk of necrotizing enterocolitis (NEC) in premature infants. We hypothesized that supplementation of formula feeds with amniotic fluid can provide amniotic fluid-borne growth factors and prevent experimental NEC in rat pups. We compared NEC-like injury in rat pups fed with infant formula vs. formula supplemented either with 30% amniotic fluid or recombinant hepatocyte growth factor (HGF). Cytokines/growth factors in amniotic fluid were measured by immunoassays. Amniotic fluid and HGF effects on enterocyte migration, proliferation, and survival were measured in cultured IEC6 intestinal epithelial cells. Finally, we used an antibody array to investigate receptor tyrosine kinase (RTK) activation and immunoblots to measure phosphoinositide 3-kinase (PI3K) signaling. Amniotic fluid supplementation in oral feeds protected rat pups against NEC-like injury. HGF was the most abundant growth factor in rat amniotic fluid in our panel of analytes. Amniotic fluid increased cell migration, proliferation, and cell survival in vitro. These effects were reproduced by HGF and blocked by anti-HGF antibody or a PI3K inhibitor. HGF transactivated several RTKs in IEC6 cells, indicating that its effects extended to multiple signaling pathways. Finally, similar to amniotic fluid, recombinant HGF also reduced the frequency and severity of NEC-like injury in rat pups. Amniotic fluid supplementation protects rat pups against experimental NEC, which is mediated, at least in part, by HGF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume306
Issue number5
DOIs
StatePublished - Mar 1 2014

Fingerprint

Necrotizing Enterocolitis
Hepatocyte Growth Factor
Amniotic Fluid
Intercellular Signaling Peptides and Proteins
1-Phosphatidylinositol 4-Kinase
Wounds and Injuries
Cytokines
Infant Formula
Antibodies
Enterocytes
Premature Birth
Receptor Protein-Tyrosine Kinases
Deglutition
Immunoassay
Premature Infants
Cell Movement
Cell Survival
Epithelial Cells

Keywords

  • Amniotic fluid
  • HGF
  • Inflammation
  • NEC
  • Phosphoinositide 3-kinase

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology
  • Medicine(all)

Cite this

Amniotic fluid-borne hepatocyte growth factor protects rat pups against experimental necrotizing enterocolitis. / Jain, Sunil; Baggerman, Eric W.; MohanKumar, Krishnan; Namachivayam, Kopperuncholan; Jagadeeswaran, Ramasamy; Reyes, Victor; Maheshwari, Akhil.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 306, No. 5, 01.03.2014.

Research output: Contribution to journalArticle

Jain, Sunil ; Baggerman, Eric W. ; MohanKumar, Krishnan ; Namachivayam, Kopperuncholan ; Jagadeeswaran, Ramasamy ; Reyes, Victor ; Maheshwari, Akhil. / Amniotic fluid-borne hepatocyte growth factor protects rat pups against experimental necrotizing enterocolitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2014 ; Vol. 306, No. 5.
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