Tet1, short for Tet-eleven translocation 1, is a dioxygenase and 5-methylcytosine hydroxylase belonging to the TET protein family of human α-ketoglutarate oxygenases. It plays a crucial role in decreasing DNA methylation abundance, maintaining DNA methylation-demethylation balance, and regulating gene expression, which is essential for genomic methylation homeostasis and epigenetic regulation [3]. It is involved in pathways like NF-κB and is important in various biological processes such as stem cell differentiation, immunity, and disease-related processes. Genetic models, especially knockout models, are valuable for studying its functions.

In THP-1 cells, knockdown of Tet1 inhibits Porphyromonas gingivalis LPS/IFN-γ-induced M1 macrophage polarization via the NF-κB pathway, reducing pro-inflammatory marker production [1]. In acute kidney injury, Tet1 knockout mice show increased renal injury, ROS accumulation, and cell cycle arrest, indicating Tet1's role in promoting SOD expression through DNA demethylation to alleviate injury [2]. In cervical cancer cells, Tet1 knockdown promotes cell proliferation, migration, invasion, and EMT, while its overexpression reverses these processes, suggesting Tet1 inhibits cervical cancer progression by regulating autophagy [4]. In a mouse model of osteoarthritis, loss of Tet1 enhances the chondrogenic potential of skeletal stem cells and leads to increased cartilage regeneration in the late stages of OA [5].

In conclusion, Tet1 is a key regulator in multiple biological processes. Model-based research, especially Tet1 knockout mouse models, has revealed its significance in diseases such as periodontal diseases, acute kidney injury, cervical cancer, and osteoarthritis. These findings contribute to a better understanding of disease mechanisms and may provide potential therapeutic targets.

References:

1. Huang, Yanlan, Tian, Cheng, Li, Qimeng, Xu, Qiong. 2019. TET1 Knockdown Inhibits Porphyromonas gingivalis LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells. In International journal of molecular sciences, 20, . doi:10.3390/ijms20082023. https://pubmed.ncbi.nlm.nih.gov/31022963/

2. Fan, Yu, Yuan, Yangmian, Xiong, Mingrui, Peng, Anlin, Zheng, Ling. 2023. Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase. In Theranostics, 13, 5348-5364. doi:10.7150/thno.87416. https://pubmed.ncbi.nlm.nih.gov/37908721/

3. Liu, Wenzheng, Wu, Guanhua, Xiong, Fei, Chen, Yongjun. 2021. Advances in the DNA methylation hydroxylase TET1. In Biomarker research, 9, 76. doi:10.1186/s40364-021-00331-7. https://pubmed.ncbi.nlm.nih.gov/34656178/

4. Ren, Ji, Chen, Xiuying, Li, Jing, Tan, Yujie, Ding, Yan. 2024. TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy. In Epigenetics, 19, 2323751. doi:10.1080/15592294.2024.2323751. https://pubmed.ncbi.nlm.nih.gov/38431880/

5. Pandey, Akshay, Hoover, Malachia, Singla, Mamta, Chan, Charles, Bhutani, Nidhi. 2023. TET1 Regulates Skeletal Stem-Cell Mediated Cartilage Regeneration. In Arthritis & rheumatology (Hoboken, N.J.), 76, 216-230. doi:10.1002/art.42678. https://pubmed.ncbi.nlm.nih.gov/37610277/