The candidate homeobox genes and their role in local-site inflammation in lip mucosa of children with non-syndromic cleft lip and palate.

Objective: Craniofacial development is a complex process which requires an expression of various genes and factors for proper facial embryogenesis. One such group of genes essential for craniofacial development is the Homeobox genes, and we have focused on the detection of DLX4, HOXB3, and MSX2 along with analyzing their role in promoting local-site inflammation using NF-κB and tissue remodelation of PTX3 in cleft lip and palate (CLP) affected tissue. Methods: Material was obtained from 15 children (aged 3--8 months) during the lip plastic. Seven controls were obtained from the lip during upper labial frenectomy. Informed consent was obtained from parents, Research Ethics Committee approval no. 5/26.08.2018. DLX4, HOXB3, MSX2 and PTX3 were detected by in situ hybridization simultaneously with the immunohistochemistry for the genes and NF-κB. Results: We found a residual gene and protein expression of DLX4 in cleft mucosa, whilst no differences in gene expression levels of HOXB3 and MSX2 were noted. A significant increase in protein expression for these genes was noted in cleft mucosa, coupled with a significant increase in NF-κB expression. No differences in PTX3 expression were noted. Conclusion: Residual expression of DLX4 via upregulation of NF-κB pathway in CLP mucosa participates in the increased cellular proliferation (stimulated also by the high HOXB3 expression) and promotion of pro-inflammatory environment. Persisting appearance of MSX2 and NF-kB in the cleft-affected lip seems to dysregulate the hard tissue formation in CLP. PTX3 gene plays a crucial role in regulation and fine-tuning the persisting inflammation in postnatal cleft-affected lip tissue. [ABSTRACT FROM AUTHOR]