PMID- 10873035
OWN - NLM
STAT- MEDLINE
DCOM- 20001016
LR  - 20161124
IS  - 0022-3468 (Print)
IS  - 0022-3468 (Linking)
VI  - 35
IP  - 6
DP  - 2000 Jun
TI  - In vitro effects of growth factors on lung hypoplasia in a model of congenital 
      diaphragmatic hernia.
PG  - 914-22
AB  - BACKGROUND/PURPOSE: Pulmonary hypoplasia, a leading contributor to the lethality 
      of congenital diaphragmatic hernia (CDH), precedes diaphragmatic malformation in 
      the nitrofen model and persists to allow experimental manipulations in organ 
      culture. Fibroblast growth factors (FGFs) are crucial to early lung development. 
      Acidic FGF (FGF-1) binds to all FGF receptors and enhances in vitro branching 
      morphogenesis. Basic FGF (FGF-2) is localized to developing airway epithelium, 
      basement membrane, and extracellular matrix. Heparin (HEP) modulates FGF kinetics 
      and inhibits smooth muscle proliferation in lung primordia. The aim of this study 
      was to examine the morphological effects of fibroblast growth factors and heparin 
      on lung hypoplasia in an organ culture model. METHODS: Sprague-Dawley rats were 
      fed nitrofen on day 9.5 of pregnancy to induce lung hypoplasia and CDH in 
      newborns. Control rats received olive oil. Normal and hypoplastic lung primordia 
      were microdissected on day 13.5 of gestation and cultured up to 78 hours in plain 
      media with or without FGF-1 or FGF-2, with or without HEP. In vitro morphological 
      development was studied by serial measurements of terminal bud count, lung area, 
      and lung perimeter. RESULTS: Over 120 fetal lung specimens were studied (n > or = 
      4 per group). Significant increases in area, perimeter, and bud count were seen 
      in normal lungs cultured with FGF-1 plus HEP compared with control media (P < 
      .05). In the nitrofen lungs, FGF1 plus HEP yielded reductions in all parameters 
      compared with those in control media (P < .05), whereas FGF-2 produced 
      significant expansion in lung area but marked reductions in bud count and lung 
      perimeter divided by square root of area (P < .05). Heparin did not produce 
      substantial or sustained alteration of morphology in normal or hypoplastic lungs. 
      CONCLUSIONS: These observations may indicate an intrinsic abnormality of FGF 
      processing in the hypoplastic nitrofen lung before diaphragmatic malformation. 
      Heparin did not rescue abnormal lung development. Mechanisms underlying the 
      differential effects of these agents now need to be explored to target fetal lung 
      growth and improve the dismal prognosis of human CDH.
FAU - Jesudason, E C
AU  - Jesudason EC
AD  - Department of Paediatric Surgery, Institute of Child Health, Alder Hey Children's 
      Hospital and The School of Biological Sciences, University of Liverpool, England.
FAU - Connell, M G
AU  - Connell MG
FAU - Fernig, D G
AU  - Fernig DG
FAU - Lloyd, D A
AU  - Lloyd DA
FAU - Losty, P D
AU  - Losty PD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
RN  - 0 (Phenyl Ethers)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 104781-85-3 (Fibroblast Growth Factor 1)
RN  - 9005-49-6 (Heparin)
RN  - N71UYG034A (nitrofen)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fibroblast Growth Factor 1/*pharmacology
MH  - Fibroblast Growth Factor 2/*pharmacology
MH  - Heparin/pharmacology
MH  - Hernia, Diaphragmatic/pathology
MH  - *Hernias, Diaphragmatic, Congenital
MH  - Lung/abnormalities/drug effects/*embryology
MH  - Organ Culture Techniques
MH  - Phenyl Ethers
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2000/06/29 11:00
MHDA- 2000/10/21 11:01
CRDT- 2000/06/29 11:00
PHST- 2000/06/29 11:00 [pubmed]
PHST- 2000/10/21 11:01 [medline]
PHST- 2000/06/29 11:00 [entrez]
AID - S0022-3468(00)17120-9 [pii]
AID - 10.1053/jpsu.2000.6919 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2000 Jun;35(6):914-22. doi: 10.1053/jpsu.2000.6919.