Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.
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.
Trovato
Maria
M
Dipartimento di Patologia Umana, Policlinico Universitario, via Consolare Valeria, 1, 98125 Messina, Italy. mariatrovato@tin.ti
D'Armiento
Maria
M
Lavra
Luca
L
Ulivieri
Alessandra
A
Dominici
Roberto
R
Vitarelli
Enrica
E
Grosso
Maddalena
M
Vecchione
Raffaella
R
Barresi
Gaetano
G
Sciacchitano
Salvatore
S
D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009436:Neural Tube Defects / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000032:analysis* / Q000502:physiology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000502:physiology
D050796:STAT3 Transcription Factor; D016159:Tumor Suppressor Protein p53; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met