Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Necrotising enterocolitis (NEC) remains an overwhelming gastrointestinal (GI) emergency in premature infants, with an annual incidence of 350 cases and a mortality of 23% in the United Kingdom. The aetiology of NEC is multifactorial and its pathogenesis poorly understood. It is characterised by severe necrotic damage to the intestine. Mucus is an adherent, viscoelastic gel layer protecting the delicate underlying epithelium from lumenal aggressors such as digestive enzymes and bacterial toxins. The group of trefoil factor peptides (TFF1-3) are part of the protective mechanism operating in the intestinal mucosa and play a fundamental role in epithelial protection, repair, and restitution. These secreted peptides have been identified in a site-specific pattern in the GI mucosa, and their expression has been shown to be upregulated in early stages of mucosal repair. The role of trefoil peptides in neonatal mucosal protection has not been well investigated. Impaired mucosal regeneration due in part to failure of upregulation of TFF expression may contribute to the pathogenesis of NEC. The aim of this study was to investigate TFF1-3 mRNA expression and to identify the gene product in the GI tracts of normal neonatal controls and infants with NEC. Parents of all babies having a laparotomy in the neonatal period (defined as up to 44 weeks' gestation) and bowel resection were approached for written consent. Bowel samples were fixed in formalin and then embedded in paraffin in an RNAse-free manner. In situ hybridisation and immunohistochemistry were performed to examine the pattern of trefoil mRNA expression and to localise the peptides in the neonatal GI tract. Forty neonatal bowel specimens were examined. Twelve patients had NEC, eight were recovering from NEC, and 20 control specimens were obtained. TFF1 and TFF2 mRNA expression were not detected in the majority of NEC specimens, and there was a relative downregulation of TFF3 expression in 83% of NEC patients. TFF1 and TFF2 expression were noted in the recovery phase from NEC. Immunohistochemistry revealed a decrease in TFF3 gene product in sites adjacent to mucosal damage secondary to NEC. In acute NEC there was no apparent expression of TFF1 and 2 protein. In the group of patients recovering from NEC, TFF1 and 2 expression were seen in association with regenerative changes in the mucosa. Previous data has shown TFF1-3 to be upregulated in the acute phase response to mucosal injury in the gut. Trefoil peptides have been shown to promote epithelial cell migration and protect against apoptosis. Our results suggest that there is a lack of TFF expression in response to NEC in the premature gut. This may lead to impaired restitution of the mucosa and contribute to the cascade of bowel necrosis and generalised sepsis characteristic of NEC.
 ...
PMID:Impaired mucosal regeneration in neonatal necrotising enterocolitis. 1557 91

We measured concentrations of the gastrointestinal protective peptides Trefoil factors in human milk. By the use of in-house ELISA we detected high amounts of TFF3, less TFF1 and virtually no TFF2 in human breast milk obtained from 46 mothers with infants born extremely preterm (24-27 wk gestation), preterm (28-37 wk gestation), and full term (38-42 wk gestation). Samples were collected during the first, second, third to fourth weeks and more than 4 wks postpartum. Median (range) TFF1 [TFF3] concentrations in human milk were 320 (30-34000) [1500 (150-27,000)] pmol/L in wk 1, 120 (30-720) [310 (50-7100)] pmol/L in wk 2, 70 (20-670) [120 (20-650)] pmol/L in wks 3 to 4, and 60 (30-2500) [80 (20-540)] pmol/L in >4 wks after delivery. The lowest concentrations of TFF1 and TFF3 were found later than 2 wks after birth. In conclusion, TFF was present in term and preterm human milk with rapidly declining concentrations during the first weeks post partum. The clinical significance of TFF present in human milk remains to be explored, both regarding development of the fetal gut and protection against necrotizing enterocolitis.
 ...
PMID:Trefoil factors in human milk. 1850 57