Gbp5, guanylate-binding protein 5, belongs to the GTPase subfamily and is mainly induced by interferon-γ (IFN-γ). It is involved in multiple cellular processes such as inflammasome activation, innate immunity, and regulation of cellular inflammatory responses [6]. It is associated with pathways like NF-κB and NLRP3 inflammasome-related signaling pathways [1,2,3,7].

In rosacea-like skin inflammation, macrophage depletion ameliorated the inflammation, and Gbp5 was identified as a hub gene associated with macrophage infiltration. Silencing Gbp5 attenuated the inflammation and suppressed M1 macrophage polarization via the NF-κB signaling pathway [1]. In osteoarthritis, Gbp5 expression increased in TNF-α-induced chondrocytes and in OA mouse and human cartilage. Knockout of Gbp5 reduced chondrocyte injury, as Gbp5 promoted chondrocyte pyroptosis through the NLRP3 inflammasome signaling pathway [2]. In collagen-induced arthritis, sinomenine, by binding to Gbp5, downregulated P2X7R and suppressed NLRP3-related pathways [3]. In liver injury, knockout of Gbp5 ameliorated D-galactosamine/lipopolysaccharide-induced injury, while liver-specific overexpression induced injury as Gbp5 promoted hepatocyte apoptosis [4]. In glioblastoma, silencing Gbp5 impaired tumor growth, and overexpression promoted malignancy via the Src/ERK1/2/MMP3 pathway [5]. In lupus nephritis, knockdown of Gbp5 in MRL/lpr mice prevented disease progression by suppressing NLRP3 inflammasome activation [7].

In conclusion, Gbp5 plays a significant role in various disease conditions. Gene knockout models, especially in mice, have been crucial in revealing its functions in promoting inflammation, cell death, and disease progression in conditions like rosacea, osteoarthritis, arthritis, liver injury, glioblastoma, and lupus nephritis. These findings highlight Gbp5 as a potential therapeutic target 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/