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Fibroblast growth factor signaling in the developing tracheoesophageal fistula.
- Source :
-
Journal of pediatric surgery [J Pediatr Surg] 2003 Mar; Vol. 38 (3), pp. 474-7; discussion 474-7. - Publication Year :
- 2003
-
Abstract
- Background/purpose: The Adriamycin-induced rat model of esophageal atresia and tracheoesophageal fistula (EA/TEF) provides a reliable system for the study of EA/TEF pathogenesis. The authors previously hypothesized that faulty branching lung morphogenesis pathways were a critical component of its pathogenesis. The authors have found evidence for faulty fibroblast growth factor (FGF) signaling related to epithelial-mesenchymal interactions in the fistula tract. To better define FGF signaling, the differential expression of FGF ligands and their receptors between lung, fistula tract, and esophagus are described.<br />Methods: Time-dated pregnant, Sprague-Dawley rats were injected with Adriamycin (2 mg/kg intraperitoneally) on days 6 through 9 of gestation. Tissues were processed for histology and reverse transcriptase polymerase chain reaction. FGF-1, -7 and -10 were measured from whole lung, fistula tract, and esophagus of TEF or normal embryos. Expression of FGF2RIIIb and FGF2RIIIc receptors was measured in isolated epithelium and mesenchyme of lung and fistula tract of TEF embryos as well as lung and esophagus from normal controls.<br />Results: FGF-1 mRNA was present in the fistula tract and normal and Adriamycin-exposed lung but absent from whole esophagus. Interestingly, FGF-7 mRNA was present only in normal lung. FGF-10 was present in all tissues examined. FGF2RIIIb mRNA was absent in fistula mesenchyme but present in all other tissues examined. However, the splice variant FGF2RIIIc mRNA was present in all tissues examined.<br />Conclusions: These findings support defective FGF signaling in the rat model of EA/TEF. Absence of FGF-7 mRNA in Adriamycin-exposed tissues suggests the primary effect of Adriamycin may be to inhibit FGF-7 expression. Moreover, absence of FGF2RIIIb in fistula mesenchyme may be caused by loss of positive feedback from FGF-7, its normal obligate ligand. Understanding these specific defects in FGF signaling may provide insight into faulty mechanisms of EA/TEF.<br /> (Copyright 2003, Elsevier Science (USA). All rights reserved.)
- Subjects :
- Abnormalities, Drug-Induced etiology
Abnormalities, Drug-Induced metabolism
Abnormalities, Drug-Induced pathology
Abnormalities, Multiple chemically induced
Abnormalities, Multiple metabolism
Abnormalities, Multiple pathology
Animals
Disease Models, Animal
Epithelium metabolism
Esophageal Atresia chemically induced
Esophageal Atresia embryology
Esophagus embryology
Esophagus metabolism
Female
Fetal Proteins biosynthesis
Fetal Proteins genetics
Fibroblast Growth Factor 7
Fibroblast Growth Factors biosynthesis
Fibroblast Growth Factors deficiency
Fibroblast Growth Factors genetics
Lung embryology
Lung metabolism
Mesoderm chemistry
Morphogenesis drug effects
Pregnancy
Rats
Rats, Sprague-Dawley
Receptor, Fibroblast Growth Factor, Type 2
Receptors, Fibroblast Growth Factor biosynthesis
Receptors, Fibroblast Growth Factor deficiency
Receptors, Fibroblast Growth Factor genetics
Reverse Transcriptase Polymerase Chain Reaction
Trachea embryology
Trachea metabolism
Tracheoesophageal Fistula chemically induced
Tracheoesophageal Fistula embryology
Abnormalities, Drug-Induced genetics
Abnormalities, Multiple genetics
Doxorubicin toxicity
Esophageal Atresia genetics
Fetal Proteins physiology
Fibroblast Growth Factors physiology
Gene Expression Regulation, Developmental drug effects
Receptors, Fibroblast Growth Factor physiology
Tracheoesophageal Fistula genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1531-5037
- Volume :
- 38
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of pediatric surgery
- Publication Type :
- Academic Journal
- Accession number :
- 12632370
- Full Text :
- https://doi.org/10.1053/jpsu.2003.50082