Itgb2-KO Mouse

Itgb2, also known as integrin beta 2, is a crucial coordinator of extracellular and intracellular signaling. Integrins play important roles in various biological processes such as cell adhesion, migration, and signal transduction. Itgb2 is involved in pathways like PI3K/AKT/mTOR [1]. It is of great biological importance as it is known to be important for host defense [1]. Genetic models, like KO/CKO mouse models, could potentially be valuable for studying its functions.

In oral squamous cell carcinoma (OSCC), CAFs with higher Itgb2 expression promote OSCC proliferation by regulating PI3K/AKT/mTOR pathways to enhance glycolysis activity, and the lactate derived from these CAFs is metabolized in OSCC cells to produce ATP via mitochondrial oxidative phosphorylation [1]. In non-small cell lung cancer, lncRNA Itgb2-AS1, which is positively correlated with Itgb2, promotes cisplatin resistance by inhibiting ferroptosis via activating the FOSL2/NAMPT axis [2]. In severe acute pancreatitis-related acute lung injury, extracellular vesicles overexpressing Itgb2 can attenuate pulmonary inflammation and endothelial cell barrier disruption [3]. In cerebral ischemia-reperfusion injury, Itgb2+ microglia subclusters have time-specific functions in energy metabolism, cell cycle, angiogenesis, neuronal myelin formation, and repair [4]. In glioblastoma, activation of Itgb2 in microglia promotes the mesenchymal transition of GBM cells through JAK1/STAT3/IL-6 signaling feedback [5]. In diabetic nephropathy, Itgb2 is up-regulated and may serve as a diagnostic marker [6]. In inflammatory bowel disease, Itgb2 is up-regulated in the IBD mouse model, and its suppression alleviates inflammation; it may also be a diagnostic marker for IBD-associated CRC [7]. In BAP1-mutated uveal melanoma, the Itgb2-ICAM1 axis promotes liver metastasis by preserving hypoxia-and ECM-related signatures [8]. In gliomas, Itgb2 is elevated in higher malignancy cases, predicts poor prognosis, and patients with high Itgb2 expression have a better immunotherapy response [9]. In premature infants with necrotizing enterocolitis, there is a trend of increased ITGB2 variants proportionately with increasing NEC severity in extremely low birthweight infants [10].

In conclusion, Itgb2 is essential for coordinating extracellular and intracellular signaling, playing important roles in multiple disease conditions including cancer, inflammation-related diseases, and ischemia-reperfusion injury. Studies using various models, though not all explicitly KO/CKO mouse models, have revealed its diverse functions in these disease areas, helping to understand disease mechanisms and potentially providing new therapeutic targets.

References:

1. Zhang, Xiaoxin, Dong, Yingchun, Zhao, Mengxiang, Hu, Qingang, Ni, Yanhong. 2020. ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system. In Theranostics, 10, 12044-12059. doi:10.7150/thno.47901. https://pubmed.ncbi.nlm.nih.gov/33204328/

2. Chen, Huiyong, Wang, Linhui, Liu, Jingting, Liao, Hongliang, Wan, Renping. . LncRNA ITGB2-AS1 promotes cisplatin resistance of non-small cell lung cancer by inhibiting ferroptosis via activating the FOSL2/NAMPT axis. In Cancer biology & therapy, 24, 2223377. doi:10.1080/15384047.2023.2223377. https://pubmed.ncbi.nlm.nih.gov/37370246/

3. Hu, Qian, Zhang, Shu, Yang, Yue, Lyon, Christopher J, Wan, Meihua. 2023. Extracellular Vesicle ITGAM and ITGB2 Mediate Severe Acute Pancreatitis-Related Acute Lung Injury. In ACS nano, 17, 7562-7575. doi:10.1021/acsnano.2c12722. https://pubmed.ncbi.nlm.nih.gov/37022097/

4. Zeng, Fanning, Cao, Jun, Hong, Zexuan, Zou, Xin, Tao, Tao. 2023. Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model. In Frontiers in immunology, 14, 1114663. doi:10.3389/fimmu.2023.1114663. https://pubmed.ncbi.nlm.nih.gov/37063847/

5. Xie, Han, Jiang, Yanyi, Xiang, Yufei, Tian, Dasheng, Bian, Erbao. . Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia. In Neuro-oncology, 26, 1438-1452. doi:10.1093/neuonc/noae065. https://pubmed.ncbi.nlm.nih.gov/38554116/

6. Xu, Mingming, Zhou, Hang, Hu, Ping, Liu, Li, Liu, Xiaoqiang. 2023. Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning. In Frontiers in immunology, 14, 1084531. doi:10.3389/fimmu.2023.1084531. https://pubmed.ncbi.nlm.nih.gov/36911691/

7. Xu, Rong, Du, Wei, Yang, Qinglong, Du, Ashuai. . ITGB2 related to immune cell infiltration as a potential therapeutic target of inflammatory bowel disease using bioinformatics and functional research. In Journal of cellular and molecular medicine, 28, e18501. doi:10.1111/jcmm.18501. https://pubmed.ncbi.nlm.nih.gov/39088353/

8. Li, Jiaoduan, Cao, Dongyan, Jiang, Lixin, Zhuang, Ai, Xiang, Dongxi. 2023. ITGB2-ICAM1 axis promotes liver metastasis in BAP1-mutated uveal melanoma with retained hypoxia and ECM signatures. In Cellular oncology (Dordrecht, Netherlands), 47, 951-965. doi:10.1007/s13402-023-00908-4. https://pubmed.ncbi.nlm.nih.gov/38150154/

9. Xu, Houshi, Zhang, Anke, Han, Xiaying, Wang, Wei, Lou, Meiqing. 2021. ITGB2 as a prognostic indicator and a predictive marker for immunotherapy in gliomas. In Cancer immunology, immunotherapy : CII, 71, 645-660. doi:10.1007/s00262-021-03022-2. https://pubmed.ncbi.nlm.nih.gov/34313821/

10. George, Lovya, Menden, Heather, Xia, Sheng, Farrow, Emily, Sampath, Venkatesh. . ITGB2 (Integrin β2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis. In Journal of pediatric gastroenterology and nutrition, 72, e37-e41. doi:10.1097/MPG.0000000000002941. https://pubmed.ncbi.nlm.nih.gov/32925548/