Correlation of the expression of YY1 and Fas cell surface death receptor with apoptosis of peripheral blood mononuclear cells, and the development of multiple organ dysfunction in children with sepsis.

Abstract

Multiple organ dysfunction (MOD) is a lethal complication in children with sepsis. Apoptosis of several cell types is involved in this process, and it is associated with increased Fas cell surface death receptor (Fas) expression. As YY1 transcription factor (YY1) negatively regulates the expression of Fas in cancer models, and is associated with the clinical outcome, it may be important in MOD. The present study aimed to determine the association between the expression of Fas, YY1 and apoptosis in children with sepsis, and its association with MOD, these factors were analyzed in 30 pediatric patients that had been diagnosed with sepsis. Peripheral blood mononuclear cells were purified from patients, and YY1 and Fas protein expression was assessed by immunocytochemistry. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick‑end labeling. Sepsis was monitored using clinical parameters, pediatric logistic organ dysfunction (PELOD) score and the pediatric mortality index. The results demonstrated that Fas expression was directly correlated with apoptosis levels and the expression of YY1 was inversely correlated with apoptosis levels. Patients with high levels of apoptosis exhibited increased disease severity and poor clinical outcome. Notably, the findings of the present study demonstrated that there were higher survival rates in patients with high YY1 expression, compared with those with low YY1 expression. Additionally, patients with MOD exhibited lower proportions of apoptotic cells compared with sepsis patients without MOD. Furthermore, the PELOD score was positively correlated with Fas and inversely correlated with YY1 expression. Finally, high apoptosis and low YY1 expression were prognostic factors associated with poor survival rates. These data suggested that YY1 may be important for apoptosis induction via the regulation of Fas during sepsis. Therefore, Fas may be a potential therapeutic target to prevent MOD through regulation of YY1 expression. Furthermore, YY1 and Fas expression in PBMCs may be used to as prognostic markers.

• Authors: Judith Reséndiz-Martínez, Juan Asbun-Bojalil, Sara Huerta-Yepez, Mario Vega
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 15 Issue 5 Pg. 2433-2442 (May 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28447715 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• FAS protein, human
• YY1 Transcription Factor
• YY1 protein, human
• fas Receptor

Topics

• Adolescent
• Apoptosis
• Child
• Child, Preschool
• Female
• Gene Expression Regulation
• Humans
• Infant
• Leukocytes, Mononuclear (metabolism, pathology)
• Male
• Multiple Organ Failure (blood, mortality, pathology)
• Sepsis (blood, mortality, pathology)
• YY1 Transcription Factor (biosynthesis)
• fas Receptor (biosynthesis)