Dact2, also known as Disheveled-associated antagonist of beta-catenin 2, is a key regulator in multiple signaling pathways. It can affect the Wnt/β -catenin and TGF -β signaling pathways by regulating target protein phosphorylation levels, playing a crucial role in tissue development, injury response, and fibrosis-related processes [1,2,3,4,5]. Zebrafish and mouse models are valuable for studying Dact2 function [2].

In zebrafish, Dact2 knockout enhanced the expression of genes related to tumor invasion, migration, and epithelial-mesenchymal transition (EMT), also accelerating wound healing [2]. In mouse models of pulmonary fibrosis, AAV6-mediated Dact2 overexpression attenuated fibrosis by promoting lysosome-mediated LDHA degradation and suppressing glycolysis in lung myofibroblasts [3]. In liver fibrosis models, the dact2 gene inhibited the activation of HSC-T6 cells and reduced the expression of TGF-β 1 [5]. Moreover, in cisplatin-induced nephrotoxicity mouse models, Dact2 knockout alleviated renal injury possibly through the Igf1-MAPK axis associated with Wnt/β-catenin signaling [6].

In conclusion, Dact2 is an important regulator in the Wnt/β-catenin and TGF-β signaling pathways, influencing processes like fibrosis, EMT, and cell proliferation. Gene knockout models in zebrafish and mice have revealed its role in various disease conditions such as pulmonary fibrosis, liver fibrosis, and cisplatin-induced nephrotoxicity, providing insights into potential therapeutic targets.

References:

1. Luo, Bairu, Zheng, Rui, Shi, Chaoqun, Xu, Guangtao, Hu, Bo. 2024. DACT2 modulates atrial fibrillation through TGF/β and Wnt signaling pathways. In Heliyon, 10, e36050. doi:10.1016/j.heliyon.2024.e36050. https://pubmed.ncbi.nlm.nih.gov/39224277/

2. Kim, Dong Hee, Kim, Eun Ji, Kim, Do Hee, Park, Seung Woo. 2020. Dact2 is involved in the regulation of epithelial-mesenchymal transition. In Biochemical and biophysical research communications, 524, 190-197. doi:10.1016/j.bbrc.2019.12.090. https://pubmed.ncbi.nlm.nih.gov/31983425/

3. Lai, Xiaofan, Huang, Shaojie, Lin, Yingying, Huang, Wenqi, Wang, Zhongxing. 2022. DACT2 protects against pulmonary fibrosis via suppressing glycolysis in lung myofibroblasts. In International journal of biological macromolecules, 226, 291-300. doi:10.1016/j.ijbiomac.2022.11.324. https://pubmed.ncbi.nlm.nih.gov/36481337/

4. Hou, Jian, Huang, Shaojie, Long, Yan, Li, Jiawen, Wu, Zhongkai. . DACT2 regulates structural and electrical atrial remodeling in atrial fibrillation. In Journal of thoracic disease, 12, 2039-2048. doi:10.21037/jtd-19-4206. https://pubmed.ncbi.nlm.nih.gov/32642106/

5. Huang, Shen'an, Qian, Xia, Jiang, Ting, Xiong, Ming, Wen, Zhili. 2022. Mechanism of dact2 gene inhibiting the occurrence and development of liver fibrosis. In Cellular and molecular biology (Noisy-le-Grand, France), 67, 33-39. doi:10.14715/cmb/2021.67.6.5. https://pubmed.ncbi.nlm.nih.gov/35818217/

6. Kim, Changuk, Kwak, Woori, Won, Dong-Hoon, Park, Jun Won, Yun, Jun-Won. 2023. Loss of Dact2 alleviates cisplatin-induced nephrotoxicity through regulation of the Igfl-MAPK pathway axis. In Cell biology and toxicology, 39, 3197-3217. doi:10.1007/s10565-023-09827-4. https://pubmed.ncbi.nlm.nih.gov/37603122/