Tgfbi, also known as transforming growth factor-β-induced gene, encodes an extracellular matrix protein, TGFBIp. TGFBIp is the second most abundant protein in the corneal stroma and is regulated by TGF-β. It is involved in multiple biological processes, and its mutations are associated with various diseases, highlighting its overall biological importance. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions [2].

In a developed TGFBI-floxed mouse model, disruption of Tgfbi in macrophages inhibited their polarization to the M2 phenotype and the macrophages-mediated stimulation on pancreatic cancer growth. It also improved anti-tumor immunity and sensitized pancreatic cancer to chemotherapy, suggesting Tgfbi in macrophages as a potential therapeutic target for pancreatic cancer [1]. In the MMTV-PyMT model of mammary gland tumorigenesis crossed with a TgfbiΔ/Δ mouse, deletion of Tgfbi led to a decrease in cancer stem cell content and lung metastasis in breast cancer, revealing its role in promoting breast cancer metastasis [3].

In conclusion, Tgfbi plays crucial roles in multiple biological processes. Model-based research, especially using KO/CKO mouse models, has revealed its significance in diseases like pancreatic and breast cancer. These findings contribute to understanding disease mechanisms and developing potential therapeutic strategies targeting Tgfbi in these disease areas.

References:

1. Zhou, Jing, Lyu, Nan, Wang, Qiongling, Staveley-O'Carroll, Kevin F, Li, Guangfu. 2023. A novel role of TGFBI in macrophage polarization and macrophage-induced pancreatic cancer growth and therapeutic resistance. In Cancer letters, 578, 216457. doi:10.1016/j.canlet.2023.216457. https://pubmed.ncbi.nlm.nih.gov/37865162/

2. Nielsen, Nadia Sukusu, Poulsen, Ebbe Toftgaard, Lukassen, Marie V, Hjortdal, Jesper, Enghild, Jan J. 2020. Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies. In Progress in retinal and eye research, 77, 100843. doi:10.1016/j.preteyeres.2020.100843. https://pubmed.ncbi.nlm.nih.gov/32004730/

3. Fico, Flavia, Santamaria-Martínez, Albert. 2020. TGFBI modulates tumour hypoxia and promotes breast cancer metastasis. In Molecular oncology, 14, 3198-3210. doi:10.1002/1878-0261.12828. https://pubmed.ncbi.nlm.nih.gov/33080107/