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Pediatric Surgery International

Published in:

01-02-2013 | Original Article

Abnormal control of lung branching in experimental esophageal atresia

Authors: Ana Catarina Fragoso, Rosa Aras-Lopez, Leopoldo Martinez, José Estevão-Costa, Juan A. Tovar

Published in: Pediatric Surgery International | Issue 2/2013

Abstract

Purpose

Esophageal atresia and tracheo-esophageal fistula (EA-TEF) result from abnormal division of the foregut into esophagus and trachea thus, it may influence airway branching and lung development. The present study examined lung morphogenesis in fetuses with EA-TEF focusing in the expression of FGF10 and its receptor FGFR2 IIIb.

Methods

Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle on E7, E8 and E9. Embryos were recovered at E15, E18 and E21 and lungs processed for immunohistochemistry and RT-PCR. Three groups were studied: control, adriamycin-exposed with EA-TEF, and adriamycin-exposed without EA-TEF. Comparisons were performed with Mann–Whitney or t tests (significance level, 5 %).

Results

Lung weight at E15 and E18 were significantly lower in adriaEA fetuses in which the relative mRNA levels of FGF10 were significantly higher. These differences disappeared near term. The receptor FGFR2 IIIb messenger was only significantly increased in adria noEA fetuses at E15. Immunohistochemical study was consistent with these findings.

Conclusions

Abnormal expression of FGF10 during earlier stages of development, when the lungs are smaller than controls, suggests a compensatory response aimed at “catching up” delayed tracheobronchial branching. Whether similar changes take place in the human condition and influence respiratory physiology remain to be determined.

Diez-Pardo J, Baoquan Q, Navarro C, Tovar JA (1996) A novel rodent experimental model of esophageal atresia and tracheoesophageal fistula: preliminary report. J Pediatr Surg 31:498–502PubMedCrossRef

Xiaomei L, Aras-Lopez R, Martinez L, Tovar JA (2012) Lung hypoplasia in rats with esophageal atresia and tracheo-esophageal fistula. Pediatr Res 71:235–240PubMedCrossRef

El-Gohary Y, Gittes GK, Tovar JA (2012) Congenital anomalies of the esophagus. Semin Pediatr Surg 19:186–193CrossRef

Sanchez-Esteban J, Wang Y, Cicchiello LA, Rubin LP (2002) Pre- and postnatal development, maturation, and plasticity. Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 282:448–456

Helve O, Pitkänen O, Janér C, Andersson S (2009) Pulmonary fluid balance in the human newborn infant. Neonatology 95:347–352PubMedCrossRef

Joshi S, Kotecha S (2007) Lung growth and development. Early Hum Dev 83:789–794PubMedCrossRef

Warburton D, Schwarz M, Tefft D, Flores-Delgado G, Anderson KKD, Cardoso WV (2000) The molecular basis of lung morphogenesis. Mech Dev 92:55–81PubMedCrossRef

Cardoso WV (2001) Molecular regulation of lung development. Annu Rev Physiol 63:471–494PubMedCrossRef

Cardoso WV, Lü J (2006) Regulation of early lung morphogenesis: questions, facts and controversies. Development 133:1611–1634PubMedCrossRef

10.

Ware LB, Matthay M (2002) Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair. Am J Physiol Lung Cell Mol Physiol 282:924–940

11.

Kumar VH, Ryan RM (2004) Growth factors in the fetal and neonatal lung. Front Biosci 9:464–480PubMedCrossRef

12.

Chuang PT, McMahon AP (2003) Branching morphogenesis of the lung: new molecular insights into an old problem. Trends Cell Biol 13:86–91PubMedCrossRef

13.

Bellusci S, Grindley J, Emoto H, Itoh N, Hogan BLM (1997) Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development 124:4867–4878PubMed

14.

Moerlooze L, Spencer-Dene B, Revest JM, Hajihosseini M, Rosewell I, Dickson C (2000) An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Developement 127:483–492

15.

Peters K, Werner S, Liao X, Wert S, Whitsett J, William L (1994) Targeted expression of a dominant negative FGF receptor blocks branching morphogenesis and epithelial differentiation of the mouse lung. EMBO J 13:3296–3301PubMed

16.

Hajduk P, Murphy P, Puri P (2010) FGF10 gene expression is delayed in the embryonic lung mesenchyme in the adriamycin mouse model. Pediatr Surg Int 26:23–27PubMedCrossRef

17.

Acosta JA, Thébaud B, Castillo C, Mailleux A, Tefft D, Wuenschell C, Anderson KD, Bourbon J, Thiery JP, Bellusci S, Warbuton D (2001) Novel mechanisms in murine nitrofen-induced pulmonary hypoplasia: FGF10 rescue in culture. Am J Physiol Lung Cell Mol Physiol 281:250–257

18.

Cilley RE, Zgleszewski SE, Chinoy MR (2000) Fetal lung development:airway pressure enhances the expression of developmental genes. J Pediatr Surg 35:113–119PubMedCrossRef

19.

Cardoso WV, Itoh A, Nogawa H, Mason I, Brody J (1997) FGF-1 and FGF-7 Induce distinctive patterns of growth and differentiation in embryonic lung epithelium. Dev Dyn 208:398–405PubMedCrossRef

20.

Montedonico S, Díez-Pardo JA, Lassaletta L, Tovar JA (1999) Respiratory malformations associated with esophageal atresia. Cir Pediatr 12:61–64PubMed

21.

de Jong EM, Felix JF, Deurloo JA, van Dooren MF, Aronson DC, Torfs CP, Heij HA, Tibboel D (2008) Non-VACTERL-Type anomalies are frequent in patients with esophageal atresia/tracheo-esophageal fistula and full or partial VACTERL association. Birth Defects Res A Clin Mol Teratol 82:92–97PubMedCrossRef

22.

Usui N, Kamata S, Ishikawa S, Sawai T, Okuyama H, Imura K, Okada A (1996) Anomalies of the tracheobronchial tree in patients with esophageal atresia. J Pediatr Surg 31:258–262PubMedCrossRef

23.

Legrand C, Michaud L, Salleron J, Neut D, Sfeir R, Thumerelle C, Bonnevalle M, Turck D, Gottrand F (2012) Long-term outcome of children with oesophageal atresia type III. Arch Dis Child 97(9):808–811. doi:10.1136/archdischild-2012-301730 PubMedCrossRef

24.

Gadzinsky V, Jönsson L, Ekerljung L, Friberg LG, Wennergren G (2011) Long-term respiratory symptoms following oesophageal atresia. Acta Pediatr 100:1222–1225CrossRef

25.

Sistonen SJ, Pakarinen M, Rintala R (2011) Long-term results of esophageal atresia: Helsinki experience and review of literature. Pediatr Surg Int 27:1141–1149PubMedCrossRef

26.

Lilja HE, Wester T (2008) Outcome in neonates with esophageal atresia treated over the last 20 years. Pediatr Surg Int 24:531–536PubMedCrossRef

27.

Sistonen S, Malmberg P, Malmström K, Haahtela T, Sarna S, Rintala RJ, Pakarinen MP (2010) Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults. Eur Respir J 36:1106–1112PubMedCrossRef

Title: Abnormal control of lung branching in experimental esophageal atresia
Authors: Ana Catarina Fragoso
Rosa Aras-Lopez
Leopoldo Martinez
José Estevão-Costa
Juan A. Tovar
Publication date: 01-02-2013
Publisher: Springer-Verlag
Published in: Pediatric Surgery International / Issue 2/2013
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-012-3195-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abnormal control of lung branching in experimental esophageal atresia

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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