Dclk1, or Doublecortin-like kinase 1, is a microtubule-associated protein kinase. It is involved in neurogenesis and has been implicated in multiple biological processes. In cancer, it serves as a stem cell marker, regulating tumorigenesis, epithelial-mesenchymal transformation, DNA damage response, and tumor immune evasion through pathways like Notch, Wnt/β-catenin, and RAS [3,4].

In atherosclerosis, macrophage-specific Dclk1 deletion in ApoE-/-mice fed a high-fat diet (HFD) attenuated the disease by reducing inflammation. Mechanistically, Dclk1 in macrophages binds to IKKβ, phosphorylates it at S177/181, activates the NF-κB signaling pathway, and induces inflammatory gene expression [1]. In obesity-induced cardiomyopathy, macrophage-specific Dclk1 knockout, rather than cardiomyocyte-specific knockout, protected against HFD-induced heart dysfunction, hypertrophy, and fibrosis. Dclk1 deficiency suppressed RIP2/TAK1 activation and inflammatory responses in macrophages [2].

In conclusion, Dclk1 plays crucial roles in inflammation-related diseases such as atherosclerosis and obesity-induced cardiomyopathy. Gene knockout mouse models, especially macrophage-specific conditional knockout models, have revealed its pro-inflammatory mechanisms in these diseases, highlighting Dclk1 as a potential therapeutic target for these conditions.

References:

1. Huang, Zhuqi, Shen, Sirui, Han, Xue, Wu, Gaojun, Liang, Guang. 2023. Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses. In EMBO molecular medicine, 15, e17198. doi:10.15252/emmm.202217198. https://pubmed.ncbi.nlm.nih.gov/36896602/

2. Yang, Bin, Zhao, Yunjie, Luo, Wu, Wang, Yi, Liang, Guang. 2023. Macrophage DCLK1 promotes obesity-induced cardiomyopathy via activating RIP2/TAK1 signaling pathway. In Cell death & disease, 14, 419. doi:10.1038/s41419-023-05960-4. https://pubmed.ncbi.nlm.nih.gov/37443105/

3. Lu, Qin, Feng, Hailan, Chen, Hong, Yan, Zixing, Cao, Zhiyun. 2022. Role of DCLK1 in oncogenic signaling (Review). In International journal of oncology, 61, . doi:10.3892/ijo.2022.5427. https://pubmed.ncbi.nlm.nih.gov/36148883/

4. Ye, Liu, Liu, Beibei, Huang, Jingling, Xu, Yungen, Wang, Shuping. 2023. DCLK1 and its oncogenic functions: A promising therapeutic target for cancers. In Life sciences, 336, 122294. doi:10.1016/j.lfs.2023.122294. https://pubmed.ncbi.nlm.nih.gov/38007147/