Deficiency of epithelial–mesenchymal transition causes child indirect inguinal hernia

• Published in: Journal of pediatric surgery 2020-04, Vol.55 (4), p.665-671
• Main Authors: Somuncu, Salih, Somuncu, Özge Sezin, Ballıca, Başak, Tabandeh, Babek
• Format: Article
• Language: English
• Subjects: EMT; Epigenetics; Epithelial–mesenchymal transition; Indirect inguinal hernia
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2019.06.020

Epithelial–mesenchymal transition (EMT) describes rapid changes in cellular phenotype. During EMT, epithelial cells down-modulate cell–cell adhesion, alter polarity, reorganize cytoskeleton, become isolated, motile, and resistant to anoikis. Epithelial breakdown and epithelial cell migration are the key processes involved in the obliteration of processus vaginalis. The great majority of abnormalities are because of nonobliteration or incomplete fusion of PV. We aimed to analyze the quantitative changes of epithelial genes in adult/child patients and their controls to examine differences of the genesis of these hernias. We also aimed to investigate the potential epigenetic causes of indirect inguinal hernia in adult patients. Ten adult, ten child indirect inguinal hernia sacs and ten adult, ten child parietal peritonea were used. Hernial sac samples were obtained from indirect inguinal hernia surgeries. Peritonea of adult patients who underwent open cholecystectomy for cholelithiasis via subcostal incision were included in the study as the healthy control groups. Ages of the children were selected to be between 0 and 5 whereas the age of adults was chosen as 35–55, respectively. Total RNA isolation and cDNA synthesis were made from hernia sacs and peritoneum samples. Relative Keratin 1, Keratin 15, Filaggrin2 and STAT3 expressions were analyzed via qPCR. Indirect inguinal hernia sac cells were seeded and grown in vitro. Child diseased cells were employed in immunocytochemistry (ICC) analysis for Cytokeratin 15, Filaggrin2 and Bcl-2. Adult indirect inguinal hernia cells were examined for H3 modifications through ICC. In child indirect inguinal hernia, Keratin expressions were found higher than their controls. They were meaningfully lower than the healthy group in adult indirect inguinal hernia. Keratin 15, Keratin 1 and Filaggrin2 expressions were all correlating since they are members of related pathways. STAT3 expressions were opposite to Keratin and Filaggrin expressions suggesting that adult cells might have a switch to the mesenchymal state from the epithelial state. Adult indirect inguinal hernia samples have switched to the mesenchymal state whereas child indirect inguinal hernia samples have shown lack of transition. Irregular changes of EMT associated genes act in the progression of indirect inguinal hernia. Hence, the information on the epigenetic regulation of EMT in patients with primary inguinal hernia can aid to comprehend the pathogenesis in a