NKRF, also known as NF-κB-repressing factor, plays a significant role in the transcriptional inhibition of various specific genes. It is closely associated with the NF-κB signaling pathway, which is crucial in regulating immune responses, inflammation, and cell survival. The study of NKRF using gene knockout models, such as KO or CKO mouse models, has been instrumental in understanding its functions in different biological processes and disease conditions [1,2].

In a CF-specific NKRF-knockout (NKRF-CKO) mouse model, NKRF was found to protect against cardiac remodeling post-myocardial infarction. NKRF expression was downregulated in CFs during pathological cardiac remodeling in vivo and in response to TNF-α in vitro. NKRF-CKO mice showed worse cardiac function, increased infarct size, heart weight, and MMP2 and MMP9 expression compared to littermates. Mechanistically, NKRF inhibits human antigen R (HuR) transcription, decreasing HuR-targeted Mmp2 and Mmp9 mRNA stability [1]. Meta-analysis and experimental validations in mouse models also showed that NKRF and ZBTB17 regulate the NF-κB signaling pathway, contributing to the shared molecular mechanisms of Alzheimer's disease and atherosclerosis [2].

In conclusion, NKRF is an important regulator in the NF-κB signaling pathway. Studies using NKRF KO/CKO mouse models have revealed its protective role in cardiac remodeling post-myocardial infarction and its contribution to the shared molecular mechanisms of Alzheimer's disease and atherosclerosis. These findings highlight the significance of NKRF in understanding the pathogenesis of these diseases and potentially developing targeted therapies.

References:

1. Guo, Chenghu, Ji, Wei, Yang, Wei, Zhang, Meng, Zhang, Cheng. 2023. NKRF in Cardiac Fibroblasts Protects against Cardiac Remodeling Post-Myocardial Infarction via Human Antigen R. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2303283. doi:10.1002/advs.202303283. https://pubmed.ncbi.nlm.nih.gov/37667861/

2. Zhang, Di, Chen, Keyan, Shan, Li Shen. . Meta-analysis and transcriptomic analysis reveal that NKRF and ZBTB17 regulate the NF-κB signaling pathway, contributing to the shared molecular mechanisms of Alzheimer's disease and atherosclerosis. In CNS neuroscience & therapeutics, 30, e14683. doi:10.1111/cns.14683. https://pubmed.ncbi.nlm.nih.gov/38738952/