Deciphering the role of TNF‑α‑induced protein8‑like2 in the pathogenesis of necrotizing enterocolitis in neonatal rats.

Abstract

Neonatal necrotizing enterocolitis (NNEC) is a disease characterized by intestinal inflammation and ischemic necrosis. Despite progress having been made during decades of research, details regarding its pathophysiology remain to be elucidated. It is known that abnormal expressions of TNF-α-induced protein 8-like 2 (TIPE2) can be observed in several diseases. However, the expression of TIPE2 in necrotizing enterocolitis (NEC) rats has not been examined before. The present study aimed to describe the expression pattern of TIPE2 and its role in NNEC pathogenesis. An NEC rat model was generated and used in the present study. All rats were sacrificed when the phenotype developed and the intestine between the lower end of the duodenum and the ileocecal were collected for further study. Hematoxylin and eosin, and immunohistochemical staining, reverse transcription-quantitative PCR and western blotting analysis were used to examine the expression of TIPE2. The results showed that the average body weight was significantly decreased in the NEC group compared with the control group along with a significant decrease of TIPE2 expression. However, the expressions of phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase AKT were significantly increased in NEC rats. The correlation analysis showed that the expressions of TIPE2 and PI3K were negatively correlated with a correlation coefficient of -0.797. To further determine the association between TIPE2 and PI3K/AKT pathway, two groups of wild type Sprague Dawley rats were infected with recombinant adenovirus Ad-V and Ad-TIPE2 respectively. The results showed that the expression of TIPE2 was significantly increased among rats in the Ad-TIPE2-infected group (OE group) compared to the ones from the Ad-V-infected group (NC group). However, the mRNA and protein expressions of PI3K and AKT were significantly decreased in Ad-TIPE2-infected rates. The difference of each index between OE and NC groups was statistically significant. The present study showed that the expression of TIPE2 was downregulated in NEC rats. TIPE2 might be involved in the pathogenesis of NEC by activating the PI3K/Akt signaling pathway.