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

Fragoso, Ana Catarina; Martínez, Leopoldo; Estevão‐Costa, José; Tovar, Juan A.

doi:10.1038/pr.2014.105

Cited by 3 publications

(1 citation statement)

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“…Although several pathways (e.g. Shh, FGF10) are reported to have been altered in the lungs of fetal rats with EA-TEF [25,26], the precise mechanisms of impaired airway branching are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

Liu

et al. 2016

Cell Physiol Biochem

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Background/Aims: Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF) pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. Methods: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1) were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. Results: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. Conclusions: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA-TEF lungs.

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Section: Discussionmentioning

confidence: 99%

Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

Liu

et al. 2016

Cell Physiol Biochem

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Embryonic tongue morphogenesis in an organ culture model of mouse mandibular arches: blocking Sonic hedgehog signaling leads to microglossia

Torii

Soeno

Fujita

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

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Mouse tongue development is initiated with the formation of lateral lingual swellings just before fusion between the mediodorsal surfaces of the mandibular arches at around embryonic day 11.0. Here, we investigated the role of Sonic hedgehog (Shh) signaling in embryonic mouse tongue morphogenesis. For this, we used an organ culture model of the mandibular arches from mouse embryos at embryonic day 10.5. When the Shh signaling inhibitor jervine was added to the culture medium for 24-96 h, the formation of lateral lingual swellings and subsequent epithelial invagination into the mesenchyme were impaired markedly, leading to a hypoplastic tongue with an incomplete oral sulcus. Notably, jervine treatment reduced the proliferation of non-myogenic mesenchymal cells at the onset of forming the lateral lingual swellings, whereas it did not affect the proliferation and differentiation of a myogenic cell lineage, which created a cell community at the central circumferential region of the lateral lingual swellings as seen in vivo and in control cultures lacking the inhibitor. Thus, epithelium-derived Shh signaling stimulates the proliferation of non-myogenic mesenchymal cells essential for forming lateral lingual swellings and contributes to epithelial invagination into the mesenchyme during early tongue development.

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Developmental Anatomy and Physiology of the Esophagus

Fiorino¹,

Nurko²

2021

Pediatric Gastrointestinal and Liver Disease

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

Cited by 3 publications

References 32 publications

Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

Embryonic tongue morphogenesis in an organ culture model of mouse mandibular arches: blocking Sonic hedgehog signaling leads to microglossia

Developmental Anatomy and Physiology of the Esophagus

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