Role of matrix metalloproteinases on the development of neural tube defect

Neural Tube Defect (NTD) is one of the most common congenital malformations and has the most severe clinical features. NTD occurs during the embryogenesis because of the neural plaque fails to form neural tube. There are many different types of NTD that have different characteristics. Genetic and environmental factors play an important role in the development of NTD. Several attempts such as diet (folic acid and B vitamins supplementation) have been suggested for the prevention of NTD formation . However, these approaches are not sufficient. It is need to determine the prognostic, predictive and/or therapeutic genetic factors for the prevention of NTD. There is no any biomarker that shows the development and occurrence of NTD. The formation of the extracellular matrix (ECM) plays an important role in the migration of neural crest cells in NTD development. Matrix metalloproteinases (MMPs) play a major role in ECM organization, cell migration, cell invasion, and other cellular behavior. The role of expression and activation of MMP in NTD is unknown. The aim of this study was to investigate the role of MMP-1, -2, and 9 genes expressions in the development of human NTD. Peripheral blood samples and NTD tissues were collected from 40 new born babies diagnosed with NTD and peripheral blood samples were taken from only 4 healthy babies for control. Total RNA isolation were performed from peripheral blood and tissues samples and MMP-1,-2,-9 genes expressions were analyzed by Quantitative Real Time PCR (Q-RT-PCR). SPSS 20.0 was used for statistical analyses. Expression differences between the blood samples of patients and healthy subjects were found in terms of MMP-1, -2, -9 genes expressions. MMPs especially MMP-1 and MMP-9 genes expressions in NTD tissues were found to be 2 to 5000 times higher than peripheral blood samples. The statistical difference was determined between subtypes of NTD in terms of MMP-2 gene expression (p=0,012). No significant relationship was found between Ca+2, B12, Folat levels and development of NTD (p> 0,05). The present study showed the necessity of using of NTD tissues in the diagnosis of NTD rather than peripheral blood that emerged in NTD studies. In addition, this study is the first report that shows the important role of MMPs in the development of NTD . MMP-1, -2 ve -9 genes expressions may play a significant role in the pathogenesis of NTD..