Tbpl1-KO Mouse

Tbpl1, also known as TATA box-binding protein-like protein 1, is a transcription-related factor. It cannot bind to the TATA-box but prefers TATA-less promoters. TBPL1 shows a stronger association with TFIIA than TBP. It is required for the transcription of ribosomal protein genes containing the TCT core promoter element in Drosophila and humans. It also mediates cell cycle arrest and apoptosis [3].

In idiopathic pulmonary fibrosis (IPF) mouse models, C-MYC can activate miR-9-5p, which negatively regulates TBPL1 expression. Up-regulated C-MYC promotes pulmonary fibroblast proliferation and differentiation by inhibiting TBPL1 via miR-9-5p, triggering IPF. Inhibiting C-MYC can up-regulate TBPL1 and repress pulmonary fibrosis [1]. Fluvoxamine, a drug, alleviates bleomycin-induced lung fibrosis in mice by restraining the activation of the cGAS-STING pathway and its downstream targets including the PERK/eIF2α/c-Myc/miR-9-5p/TBPL1 signaling, attenuating fibroblast activation and migration [2].

In conclusion, TBPL1 is important in transcription regulation, especially for ribosomal protein genes. In IPF, its regulation by C-MYC and miR-9-5p plays a crucial role in the development of the disease. Mouse models have revealed its role in the context of IPF, providing insights into the disease mechanism and potential therapeutic targets.