Epsti1, or epithelial-stromal interaction 1, is an interferon response gene. It has been implicated in multiple biological processes and disease-related pathways. It plays a role in inflammation-related signaling pathways such as the NF-κB pathway and is involved in the regulation of immune-related processes, which are crucial for normal physiological functions and disease development [1,2,3,4].

In Epsti1-deficient mice, impaired muscle regeneration with elevated inflammation response was observed. Epsti1 interacts with valosin-containing protein (VCP) and mediates the proteasomal degradation of IFN-γ-activated STAT1, contributing to dampening STAT1-mediated inflammation during early muscle regeneration [1]. In the context of osteoporosis, EPSTI1 was found to be increased in osteoclasts of osteoporotic patients. Knockdown of EPSTI1 in RAW264.7 cells reduced osteoclastic resorption, suggesting it may regulate osteoclast differentiation and bone resorption through the PKR/NF-κB pathway [2]. In a cellular pneumonia model, knockdown of EPSTI1 alleviated lipopolysaccharide-induced inflammatory injury by inactivating the NF-κB pathway [4].

In conclusion, Epsti1 plays essential roles in inflammation regulation, muscle regeneration, and bone-related processes. Studies using Epsti1-deficient mouse models have revealed its significance in these biological functions, providing insights into the underlying mechanisms of related diseases such as muscle-regeneration-associated disorders, osteoporosis, and pneumonia [1,2,4].

References:

1. Kim, Jee Won, Bae, Ju-Hyeon, Go, Ga-Yeon, Kang, Jong-Sun, Bae, Gyu-Un. 2024. Epsti1 Regulates the Inflammatory Stage of Early Muscle Regeneration through STAT1-VCP Interaction. In International journal of biological sciences, 20, 3530-3543. doi:10.7150/ijbs.94675. https://pubmed.ncbi.nlm.nih.gov/38993551/

2. Zhang, Muzi, Yang, E, Qin, Xiaoyu, Fu, Hongyi, He, Bin. 2024. EPSTI1 promotes osteoclast differentiation and bone resorption by PKR/NF-κB signaling. In Biochemical and biophysical research communications, 734, 150463. doi:10.1016/j.bbrc.2024.150463. https://pubmed.ncbi.nlm.nih.gov/39083969/

3. Sun, Jin-Lei, Zhang, Hao-Ze, Liu, Su-Ying, Chen, Hua, Zhang, Feng-Chun. 2020. Elevated EPSTI1 promote B cell hyperactivation through NF-κB signalling in patients with primary Sjögren's syndrome. In Annals of the rheumatic diseases, 79, 518-524. doi:10.1136/annrheumdis-2019-216428. https://pubmed.ncbi.nlm.nih.gov/32114510/

4. Kari, Adilijiang, M, Zhihua, Aili, Zhayidan, Hairula, Nadire, Abuduhaer, Abulaiti. 2022. Knockdown of EPSTI1 alleviates lipopolysaccharide-induced inflammatory injury through regulation of NF-κB signaling in a cellular pneumonia model. In Allergologia et immunopathologia, 50, 106-112. doi:10.15586/aei.v50i3.581. https://pubmed.ncbi.nlm.nih.gov/35527663/