Vtn-KO Mouse

Vtn, also known as Vitronectin, is a protein-encoding gene. Vitronectin is involved in multiple biological processes, including cell-cell and cell-extracellular matrix (ECM) interactions, and may participate in signaling pathways related to phagocytosis, fibroblast activation, and immune responses [1,2,3]. Its study using genetic models like knockout mice can help reveal its in-vivo functions.

In tumor research, a genome-wide CRISPR screen identified Vtn as part of a ligand-receptor pair (Vtn-C1qbp) that inhibits macrophage phagocytosis of tumor cells. Tumor cell-secreted Vtn interacts with C1qbp on tumor-associated macrophages, shifting macrophages towards the M2-like subtype. Knockdown of Vtn enhanced macrophage phagocytosis and infiltration, reducing tumor growth in mouse models, suggesting it as a new anti-phagocytic signal in tumors [1].

In kidney fibrosis, Vtn was upregulated in fibrotic kidneys and primarily secreted by activated macrophages. Genetic Vtn knockout (Vtn-/-) mice were protected from developing kidney fibrosis after injury, while overexpression of Vtn exacerbated renal fibrotic lesions. Macrophage-derived Vtn-enriched ECM promoted fibroblast activation via integrin αvβ5 and Src kinase signaling [2].

In the context of idiopathic pulmonary fibrosis, knockdown of FBLN2, which binds to VTN, suppressed TGF-β1-induced MRC-5 cell migration and fibrosis by downregulating VTN, and overexpression of VTN partly abolished these inhibitory effects [4].

In conclusion, Vtn plays essential roles in tumor progression, kidney fibrosis, and pulmonary fibrosis. The use of Vtn knockout or knockdown models in mice has been crucial in understanding its functions in these disease areas, highlighting its potential as a therapeutic target for triple-negative breast cancer, fibrotic chronic kidney disease, and idiopathic pulmonary fibrosis [1,2,4].

References:

1. Zhang, Chen, Liu, Yi, Jiang, Jiayu, Xiang, Rong, Luo, Yunping. 2024. Targeting tumor cell-to-macrophage communication by blocking Vtn-C1qbp interaction inhibits tumor progression via enhancing macrophage phagocytosis. In Theranostics, 14, 2757-2776. doi:10.7150/thno.94537. https://pubmed.ncbi.nlm.nih.gov/38773982/

2. Peng, Yiling, Li, Li, Shang, Jingyue, Fu, Haiyan, Liu, Youhua. 2023. Macrophage promotes fibroblast activation and kidney fibrosis by assembling a vitronectin-enriched microenvironment. In Theranostics, 13, 3897-3913. doi:10.7150/thno.85250. https://pubmed.ncbi.nlm.nih.gov/37441594/

3. Rai, Alin, Fang, Haoyun, Claridge, Bethany, Simpson, Richard J, Greening, David W. . Proteomic dissection of large extracellular vesicle surfaceome unravels interactive surface platform. In Journal of extracellular vesicles, 10, e12164. doi:10.1002/jev2.12164. https://pubmed.ncbi.nlm.nih.gov/34817906/

4. Zhang, Yanju, Zhang, Weishuai, Zhang, Rui, Xia, Yunfei. 2022. Knockdown of FBLN2 suppresses TGF-β1-induced MRC-5 cell migration and fibrosis by downregulating VTN. In Tissue & cell, 81, 102005. doi:10.1016/j.tice.2022.102005. https://pubmed.ncbi.nlm.nih.gov/36608640/