Gpx7, also known as NPGPx, is a member of the glutathione peroxidase (GPx) family without any GPx activity [2]. It is a conserved endoplasmic reticulum (ER) retention protein, and serves as a stress sensor/transmitter, transferring signals to its interacting proteins by shuttling disulfide bonds in response to various stresses [2]. It may be involved in protein folding as it is located in the endoplasmic reticulum [7]. Gpx7 is important for maintaining redox homeostasis [2].

Gpx7 deficiency reduces osteogenesis but increases adipogenesis in both human BMSCs and mouse mesenchymal stem cell line. This defect can be alleviated by the ER stress antagonist, indicating that Gpx7-deficiency inhibits osteogenesis via induced ER stress rather than enhanced ROS. Also, the mTOR signalling pathway is down-regulated during osteogenic differentiation in Gpx7-deficient condition, which can be rescued by relief of ER stress, suggesting Gpx7 may protect against osteoporotic deficits through ER stress and mTOR pathway interplay [1]. In non-alcoholic steatohepatitis, knockdown of Gpx7 in relevant cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis, while its overexpression led to suppression of ROS production and reduced expression of these genes. Moreover, knockdown of Gpx7 accelerated NASH fibrosis induced by a specific diet in mice [3]. In chondrocytes, GPX7 level was decreased in response to IL-1β treatment, and its overexpression suppressed cellular inflammation, ECM degradation, apoptosis and ferroptosis [4]. In glioma, GPX7 silencing enhanced ferroptosis-related oxidative stress and loss of GXP7 sensitized glioma to ferroptosis induced by erastin, and miR-29b directly suppressed GPX7 expression post-transcriptionally [5]. In papillary thyroid carcinoma, knockdown of GPX7 decreased cell proliferation and increased apoptosis [6].

In summary, Gpx7 plays crucial roles in multiple biological processes and disease conditions. Gene knockout models have revealed its significance in osteogenesis, adipogenesis, non-alcoholic steatohepatitis, chondrocyte-related processes, glioma, and papillary thyroid carcinoma. These findings help in understanding the underlying mechanisms of these diseases and potentially developing new therapeutic strategies related to Gpx7-targeted interventions.

References:

1. Hu, Xuchen, Li, Boer, Wu, Fanzi, Shi, Yu, Ye, Ling. 2021. GPX7 Facilitates BMSCs Osteoblastogenesis via ER Stress and mTOR Pathway. In Journal of cellular and molecular medicine, 25, 10454-10465. doi:10.1111/jcmm.16974. https://pubmed.ncbi.nlm.nih.gov/34626080/

2. Chen, Yi-Ing, Wei, Pei-Chi, Hsu, Jye-Lin, Su, Fang-Yi, Lee, Wen-Hwa. 2016. NPGPx (GPx7): a novel oxidative stress sensor/transmitter with multiple roles in redox homeostasis. In American journal of translational research, 8, 1626-40. doi:. https://pubmed.ncbi.nlm.nih.gov/27186289/

3. Kim, Hyeon Ju, Lee, Yoseob, Fang, Sungsoon, Kim, Hyo Jung, Kim, Jae-Woo. . GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress. In BMB reports, 53, 317-322. doi:. https://pubmed.ncbi.nlm.nih.gov/32317079/

4. Chen, Boyuan, Fu, Weihao, Jie, Chunyang, Liu, Yihai, Zhou, Shibo. 2024. GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis. In Molecular medicine reports, 30, . doi:10.3892/mmr.2024.13242. https://pubmed.ncbi.nlm.nih.gov/38757339/

5. Zhou, Yan, Wu, Haiyang, Wang, Fanchen, Tong, Xiaoguang, Yan, Hua. 2022. GPX7 Is Targeted by miR-29b and GPX7 Knockdown Enhances Ferroptosis Induced by Erastin in Glioma. In Frontiers in oncology, 11, 802124. doi:10.3389/fonc.2021.802124. https://pubmed.ncbi.nlm.nih.gov/35127512/

6. Liu, Li-Dan, Zhang, Yi-Ni, Wang, Li-Fen. . GPX7 promotes the growth of human papillary thyroid carcinoma via enhancement of cell proliferation and inhibition of cell apoptosis. In Translational cancer research, 8, 2570-2580. doi:10.21037/tcr.2019.10.14. https://pubmed.ncbi.nlm.nih.gov/35117014/

7. Pei, Jun, Pan, Xingyu, Wei, Guanghui, Hua, Yi. 2023. Research progress of glutathione peroxidase family (GPX) in redoxidation. In Frontiers in pharmacology, 14, 1147414. doi:10.3389/fphar.2023.1147414. https://pubmed.ncbi.nlm.nih.gov/36937839/