Elimination of the RETNLB Gene Alleviates Intestinal Damage in NEC Mice

Abstract

Abstract Background: The most serious gastrointestinal inflammation in newborns is necrotizing enterocolitis (NEC), which progresses quickly and has a high fatality rate. Resistin related molecule β (RELMβ) is highly concentrated in the intestines of both mice and humans according to earlier studies that have linked RELMβ to a variety of intestinal inflammatory disorders. Therefore, we hypothesized that targeting the RELMβ gene may inhibit inflammation and alleviate NEC in vivo. Methods: First, RELMβ (RETNLB) knockout (KO) C57BL/6 mice were procured. Then, RETNLB KO mice and wild-type (WT) C57BL/6 mice were separated into 4 groups according to the NEC experimental model used for this study. The groups were as follows: group A consisted of WT mice, group B consisted of KO mice, group C consisted of WT mice with NEC, and Group D consisted of KO mice with NEC. Each group had 9 mice, and alterations in intestinal histology were analyzed. Expression levels of TLR2 and TLR4 in the intestinal tissues of each group were evaluated by simultaneous quantitative real-time polymerase chain reaction (qRT-PCR). Results: Compared with WT mice, the expression levels of TLR2 and TLR4 were significantly up-regulated in WT mice following induction of NEC. Post-RETNLB KO, the expression levels of TLR2 and TLR4 in the KO group decreased significantly, and the differences were determined to be statistically significant (P<0.05). Interestingly, the degree of pathological damage to the intestines of KO mice was attenuated after induction of NEC. Compared with KO mice, there was no significant difference in the expression level of TLR4 in the KO NEC group (P>0.05); however, the expression level of TLR2 was significantly up-regulated (P<0.05). Conclusion: RETNLB KO may exert a protective effect against intestinal injury in NEC mice through regulation of TLR4.