Tnfaip2, also known as tumor necrosis factor, alpha-induced protein 2, is a primary response gene of TNFα [3]. It has multiple functions, such as promoting angiogenesis, motivating the inflammatory response, facilitating cell proliferation, adhesion, migration, and inducing tunnel nanotube (TNT) formation. Its expression is regulated by multiple transcription factors and signalling pathways, including NF-κB, KLF5 and retinoic acid [3]. TNFAIP2 appears to be a multiple-functional mediator in various physiological and pathological scenarios [3].

In diabetic nephropathy, tnfaip2 deletion in mice exacerbated albuminuria, renal function loss, podocyte injury, and mesangial expansion. It also blocked autophagic flux due to lysosomal dysfunction in diabetes-injured podocytes, indicating its protective role in podocytes by allowing TNT-mediated autophagosome and lysosome exchange [1]. In head and neck squamous cell carcinoma, high expression of TNFAIP2 is associated with poor prognosis and cisplatin resistance. Knockdown of TNFAIP2 enhanced cisplatin treatment effect in a mouse model, suggesting it as a potential target for improving cisplatin treatment [2]. In atherogenesis, Tnfaip2 deficiency in bone marrow-derived cells inhibited atherosclerosis development in Ldlr-/-mice fed a high-fat diet, with decreased inflammatory cytokines, indicating its role in promoting atherogenesis through enhancing oxidative stress-induced inflammation [4].

In conclusion, Tnfaip2 is a multifunctional gene involved in many biological processes and disease conditions. Gene knockout studies in mouse models have revealed its crucial roles in diabetic nephropathy, cancer (such as head and neck squamous cell carcinoma), and atherogenesis, providing potential therapeutic targets for these diseases.

References:

1. Barutta, F, Bellini, S, Kimura, S, Ohno, H, Gruden, G. 2022. Protective effect of the tunneling nanotube-TNFAIP2/M-sec system on podocyte autophagy in diabetic nephropathy. In Autophagy, 19, 505-524. doi:10.1080/15548627.2022.2080382. https://pubmed.ncbi.nlm.nih.gov/35659195/

2. Xu, Teng, Yang, Yuemei, Chen, Zhihong, Wu, Yunong, Song, Xiaomeng. 2023. TNFAIP2 confers cisplatin resistance in head and neck squamous cell carcinoma via KEAP1/NRF2 signaling. In Journal of experimental & clinical cancer research : CR, 42, 190. doi:10.1186/s13046-023-02775-1. https://pubmed.ncbi.nlm.nih.gov/37525222/

3. Jia, Lin, Shi, Yundong, Wen, Yi, Feng, Jing, Chen, Ceshi. 2018. The roles of TNFAIP2 in cancers and infectious diseases. In Journal of cellular and molecular medicine, 22, 5188-5195. doi:10.1111/jcmm.13822. https://pubmed.ncbi.nlm.nih.gov/30145807/

4. Jin, Guiyuan, Liu, Ying, Xu, Wenwen, Gao, Chengjiang, Liu, Suxia. 2022. Tnfaip2 promotes atherogenesis by enhancing oxidative stress induced inflammation. In Molecular immunology, 151, 41-51. doi:10.1016/j.molimm.2022.08.019. https://pubmed.ncbi.nlm.nih.gov/36084515/