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Expression of p53/hgf/c-met/STAT3 signal in fetuses with neural tube defects

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Abstract

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

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Authors and Affiliations

  1. Dipartimento di Patologia Umana, Policlinico Universitario, via Consolare Valeria, 1, 98125, Messina, Italy

    Maria Trovato, Enrica Vitarelli, Maddalena Grosso & Gaetano Barresi

  2. Dipartimento di Scienze Biomorforlogica e Funzionale, Sezione di Anatomia Patologica, Università Federico II di Napoli, via Pansini Sergio, 5, 80131, Napoli, Italy

    Maria D’Armiento & Raffaella Vecchione

  3. Centro di Ricerca Ospedale S.Pietro Fatebenefratelli, AFAR, via Cassia, 450, 00189, Roma, Italy

    Luca Lavra, Alessandra Ulivieri & Salvatore Sciacchitano

  4. Istituto di Neurobiologia e Medicina Molecolare, CNR, Viale Dell’ Universita’, 11, 00185, Roma, Italy

    Roberto Dominici & Salvatore Sciacchitano

  5. Ospedale Sant’Andrea, II Facoltà di Medicina e Chirurgia, Università La Sapienza, Via di Grottarossa, 1035-1039, 00189, Roma, Italy

    Salvatore Sciacchitano

Authors
  1. Maria Trovato
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  2. Maria D’Armiento
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  3. Luca Lavra
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  4. Alessandra Ulivieri
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  5. Roberto Dominici
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  6. Enrica Vitarelli
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  7. Maddalena Grosso
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  8. Raffaella Vecchione
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  9. Gaetano Barresi
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  10. Salvatore Sciacchitano
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Corresponding authors

Correspondence to Maria Trovato or Salvatore Sciacchitano.

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Our experiments comply with the current laws of the country in which they were performed.

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Trovato, M., D’Armiento, M., Lavra, L. et al. Expression of p53/hgf/c-met/STAT3 signal in fetuses with neural tube defects. Virchows Arch 450, 203–210 (2007). https://doi.org/10.1007/s00428-006-0356-5

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  • DOI: https://doi.org/10.1007/s00428-006-0356-5

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