Gbp5, short for Guanylate-binding protein 5, is a member of the GTPase family induced by Interferon-γ (IFN-γ). It significantly influences cellular inflammatory responses, involving in intracellular inflammasome activation, cytokine release, and innate immunity against various microbial pathogens [2,6]. It has been associated with multiple signaling pathways such as NF-κB, NLRP3 inflammasome-related pathways [1,2,3,7].

In rosacea-like skin inflammation, macrophage depletion alleviated the condition, and Gbp5 was identified as a hub gene associated with macrophage infiltration. Silencing Gbp5 attenuated rosacea-like skin inflammation in mouse models by suppressing M1 macrophage polarization via the NF-κB signaling pathway [1]. In osteoarthritis, Gbp5 expression increased in TNF-α-induced chondrocytes and in the cartilage of OA mice and human patients. Gbp5 knockout reduced chondrocyte injury in OA mice, as it promoted chondrocyte pyroptosis through the NLRP3 inflammasome signaling pathway [2]. In collagen-induced arthritis, sinomenine, by competitively binding Gbp5, suppressed the Gbp5/P2X7R-NLRP3 pathways, reducing the production of inflammatory cytokines [3]. In liver injury, Gbp5 knockout ameliorated D-galactosamine/lipopolysaccharide-induced liver injury and inflammation, while its overexpression induced liver injury as it promoted hepatocyte apoptosis through multiple caspase-related pathways [4]. In glioblastoma, silencing Gbp5 by RNA interference impaired tumor growth and prolonged the survival time of mice with GBM tumors, as Gbp5 promoted the malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway [5]. In lupus nephritis, Gbp5 inhibition in MRL/lpr mice prevented the progression of the disease by suppressing NLRP3 inflammasome activation [7].

In conclusion, Gbp5 plays crucial roles in inflammation, cell death, and disease progression in various conditions including rosacea, osteoarthritis, arthritis, liver injury, glioblastoma, and lupus nephritis. Gene knockout models in mice have been instrumental in revealing these functions, providing potential therapeutic targets for these diseases.

References:

1. Zhou, Lei, Zhao, Han, Zhao, He, Tang, Yan, Zhang, Yiya. 2022. GBP5 exacerbates rosacea-like skin inflammation by skewing macrophage polarization towards M1 phenotype through the NF-κB signalling pathway. In Journal of the European Academy of Dermatology and Venereology : JEADV, 37, 796-809. doi:10.1111/jdv.18725. https://pubmed.ncbi.nlm.nih.gov/36367676/

2. Tang, Hao, Gong, Xiaoshan, Dai, Jingjin, Deng, Jiezhong, Dong, Shiwu. 2023. The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis. In Journal of orthopaedic translation, 44, 47-59. doi:10.1016/j.jot.2023.11.005. https://pubmed.ncbi.nlm.nih.gov/38229660/

3. Li, Juan-Min, Deng, Hai-Shan, Yao, Yun-da, Lu, Lin-Lin, Zhou, Hua. 2023. Sinomenine ameliorates collagen-induced arthritis in mice by targeting GBP5 and regulating the P2X7 receptor to suppress NLRP3-related signaling pathways. In Acta pharmacologica Sinica, 44, 2504-2524. doi:10.1038/s41401-023-01124-4. https://pubmed.ncbi.nlm.nih.gov/37482570/

4. Ding, Kaixin, Li, Xinzhi, Ren, Xiaomeng, Dong, Xue, Chen, Zheng. . GBP5 promotes liver injury and inflammation by inducing hepatocyte apoptosis. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22119. doi:10.1096/fj.202101448R. https://pubmed.ncbi.nlm.nih.gov/34958688/

5. Yu, Xiaoting, Jin, Jing, Zheng, Yanwen, Chen, Clark C, Li, Ming. 2021. GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway. In Cell death & disease, 12, 203. doi:10.1038/s41419-021-03492-3. https://pubmed.ncbi.nlm.nih.gov/33608513/

6. Li, Zhaolong, Qu, Xinglong, Liu, Xin, Hua, Shucheng, Zhang, Wenyan. 2020. GBP5 Is an Interferon-Induced Inhibitor of Respiratory Syncytial Virus. In Journal of virology, 94, . doi:10.1128/JVI.01407-20. https://pubmed.ncbi.nlm.nih.gov/32796072/

7. Liu, Naiquan, Gao, Yan, Liu, Ying, Liu, Dajun. 2022. GBP5 Inhibition Ameliorates the Progression of Lupus Nephritis by Suppressing NLRP3 Inflammasome Activation. In Immunological investigations, 52, 52-66. doi:10.1080/08820139.2022.2122834. https://pubmed.ncbi.nlm.nih.gov/36175170/