Estrogen is a novel regulator of Tnfaip1 in mouse hippocampus

Abstract

Tumor necrosis factor-induced protein 1 (Tnfaip1), also known as B12, has been previously identified as a tumor necrosis factor-α (TNF-α)-inducible protein and is involved in the cytokinesis signaling pathway, DNA synthesis, innate immunity, cell apoptosis, Alzheimer's disease (AD) and type 2 diabetic nephropathy. However, little is known regarding the expression of Tnfaip1 in various tissues or its accurate role in these physiological functions. The focus of this study was on Tnfaip1 expression in different tissues, with a high expression in mouse hippocampus being identified. The age- and gender-related expression of Tnfaip1 in hippocampus was also investigated. The distribution of Tnfaip1 was mapped using fluorescent immunostaining. Although immunoactivity was found in the CA1, CA3 and DG subregions of the hippocampus in E17.5 and P6 mice, strong staining was only detected in the CA3 subregion in adult mice. These data suggested that Tnfaip1 expression in hippocampus may be regulated by estrogen. Further study showed that the expression of Tnfaip1 in the hippocampus was significantly increased in ovariectomized mice compared to Sham mice. In cultured primary hippocampal cells, Tnfaip1 showed different expression levels in different treatments of estrogen or estrogen receptor antagonists. Additional experiments demonstrated the existence of a binding site of ERβ in the Tnfaip1 promoter region, and that ERβ was able to upregulate Tnfaip1 expression. Our study identified a new regulatory factor and a primary regulatory mechanism of Tnfaip1 expression in hippocampus. Since both hippocampus and estrogen are crucial in AD, the results also showed a potential association between Tnfaip1 and hippocampal-related diseases, such as AD, which may be affected by the estrogen level.