Abnormal Sonic hedgehog signaling in the lung of rats with esophageal atresia induced by adriamycin

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Fragoso AC (Autor) FMUP; Martinez L (Autor) Outra; Estevão-Costa J (Autor) FMUP; Tovar JA (Autor) Outra

Revista

Título: Pediatric Research

Vol. 76 Nº 4

Páginas: 355-362

ISSN: 0031-3998

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 3 Citações

ISI Web of Science

Scopus - 4 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde

Outras Informações

ID Authenticus: P-009-VZJ

DOI: 10.1038/pr.2014.105

Abstract (EN): BACKGROUND: Abnormal lung development was recently described in the rat model of esophageal atresia and tracheoesophageal fistula (EA-TEF). Since in this condition the ventral-to-dorsal switch of Shh expression in the foregut is disturbed, the present study tested the hypothesis that this abnormal expression at the emergence of the tracheobronchial bud might be translated into the developing lung. METHODS: Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle from E7 to E9. Three groups were studied: control and adriamycin-exposed with and without EA-TEF. Embryos were recovered and the lungs were harvested and processed for reverse transcription polymerase chain reaction and immunofluorescence analysis of the Shh signaling cascade. RESULTS: Shh signaling was downregulated at the late embryonic stage of lung development (E13) in embryos with EA-TEE Throughout the subsequent stages of development, the expression of both Shh and its downstream components increased significantly and remained upregulated throughout gestation. Immunofluorescent localization was consistent with these findings. CONCLUSION: Defective Shh signaling environment in the foregut is present beyond the emergence of lung buds and probably impairs lung development. Later in gestation, lungs exhibited a remarkable ability to upregulate the Shh cascade, suggesting a compensatory response. These findings may be relevant to understand pulmonary disease suffered by children with EA-TEF.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8