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

Area of Science:

• Developmental Biology
• Genetics
• Pathology

Background:

• Neural tube defects (NTD) are congenital malformations arising from incomplete closure of the neural tube during embryonic development.
• The hepatocyte growth factor (HGF)/c-met signaling pathway is crucial for organogenesis, including the nervous system, lungs, and kidneys.
• p53 is a tumor suppressor protein that regulates genes involved in cell cycle arrest, apoptosis, and DNA repair, including HGF and c-met.

Purpose of the Study:

• To investigate the mRNA and protein expression levels of p53, HGF, c-met, and STAT3 in fetuses diagnosed with NTD.
• To explore the potential role of the p53/HGF/c-met/STAT3 cascade in the pathogenesis of NTD.
• To assess the diagnostic potential of this pathway for early NTD detection.

Main Methods:

• Analysis of neural tissues, placentas, lungs, and kidneys from four NTD fetuses and control samples.
• Quantification of mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR).
• Assessment of protein expression via immunohistochemistry.

Main Results:

• Reduced mRNA expression of HGF, c-met, and STAT3 was observed in the malformed neural tissues and placentas of NTD fetuses.
• This reduction in the HGF/c-met/STAT3 pathway correlated with the absence of p53 expression in these affected tissues.
• Conversely, non-malformed lungs and kidneys from the same fetuses exhibited detectable levels of p53, HGF, c-met, and STAT3.

Conclusions:

• A significant reduction in the p53/HGF/c-met/STAT3 signaling cascade occurs in both the defective neural tube and placental tissues of fetuses with NTD.
• The findings suggest a potential link between the dysregulation of this pathway and NTD development.
• The suppression of these genes may serve as a biomarker for the early diagnosis of NTD, potentially through chorionic villus sampling.