Tgfb1-KO Mouse

Tgfb1, encoding TGF-β1, is a gene for a potent cytokine that regulates diverse cellular processes such as immune responses, cell growth, differentiation, and apoptosis. It is involved in multiple signaling pathways including the SMAD-dependent pathway, which is crucial for its downstream effects. TGF-β1 is of great biological importance in tissue repair, development, and disease processes [3].

In the context of intestinal regeneration, irradiation-induced damage leads to a surge in Tgfb1 expression mediated by monocyte/macrophage cells at the damage site. Depletion of macrophages or genetic disruption of TGF-β signaling significantly impairs the regenerative response. Tgfb1 treatment in organoid culture can induce a fetal-like/regenerative state, and it also activates pro-regenerative factors YAP/TEAD and SOX9 in the epithelium, suggesting its key role in enhancing intestinal regeneration [1]. In pancreatic cancer, the TGFB1/INHBA homodimer/Nodal-SMAD2/3 signaling network is a pivotal central node regulating chemoresistance mechanisms, including enhancing stem-like properties of cancer cells and mediating interactions with the stroma [2]. In hematological malignancies, Tgfb1 shows a hematologic-tissue-specific expression pattern, is broadly dysregulated, associated with adverse prognosis, and can predict immunotherapy responses [3].

In summary, Tgfb1 is essential in regulating various biological processes. Mouse models, through genetic disruption of TGF-β signaling, have revealed its significance in intestinal regeneration. In diseases, its dysregulation plays a role in pancreatic cancer chemoresistance and hematological malignancies, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Chen, Lei, Qiu, Xia, Dupre, Abigail, Spence, Jason R, Verzi, Michael P. 2023. TGFB1 induces fetal reprogramming and enhances intestinal regeneration. In Cell stem cell, 30, 1520-1537.e8. doi:10.1016/j.stem.2023.09.015. https://pubmed.ncbi.nlm.nih.gov/37865088/

2. Abdel Mouti, Mai, Pauklin, Siim. 2021. TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment. In Molecular therapy : the journal of the American Society of Gene Therapy, 29, 920-936. doi:10.1016/j.ymthe.2021.01.002. https://pubmed.ncbi.nlm.nih.gov/33429081/

3. Wang, Cui-Zhu, Zhang, Zi-Qi, Zhang, Yan, Sha, Suo, Xu, Zi-Jun. 2023. Comprehensive characterization of TGFB1 across hematological malignancies. In Scientific reports, 13, 19107. doi:10.1038/s41598-023-46552-8. https://pubmed.ncbi.nlm.nih.gov/37925591/