RGD Reference Report - Abnormal Sonic hedgehog signaling in the lung of rats with esophageal atresia induced by adriamycin. - Rat Genome Database

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

Authors: Fragoso, Ana Catarina  Martinez, Leopoldo  Estevão-Costa, José  Tovar, Juan A 
Citation: Fragoso AC, etal., Pediatr Res. 2014 Oct;76(4):355-62. doi: 10.1038/pr.2014.105. Epub 2014 Jul 8.
RGD ID: 12801416
Pubmed: PMID:25003913   (View Abstract at PubMed)
DOI: DOI:10.1038/pr.2014.105   (Journal Full-text)


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-TEF. 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Shh  (sonic hedgehog signaling molecule)

Genes (Mus musculus)
Shh  (sonic hedgehog)

Genes (Homo sapiens)
SHH  (sonic hedgehog signaling molecule)


Additional Information