Trpm7, the transient receptor potential melastatin-subfamily member 7, is a ubiquitously expressed chanzyme. It has an ion channel permeable to divalent cations like Mg2+, Ca2+, and Zn2+, and an α-kinase that phosphorylates downstream substrates [2]. It is involved in intracellular signaling, especially receptor tyrosine kinase (RTK)-mediated pathways [2]. TRPM7 is crucial for cellular and systemic magnesium homeostasis, and thus plays a key role in embryonic development, global ischemia, cardiovascular disease, and cancer [3]. Genetic models, such as gene knockout in animal models, have been instrumental in understanding its functions [4].

Genetic inactivation of Trpm7 in animal models has revealed its critical role in early embryonic development, immune responses, and the organismal balance of Zn2+, Mg2+, and Ca2+ [4]. In rheumatoid arthritis, both genetic and pharmacological inhibitions of Trpm7 attenuated articular cartilage damage and chondrocyte ferroptosis via the PKCα-NOX4 axis, suggesting it as a potential target for prevention and treatment [1]. In ovarian cancer, its overexpression is linked to adverse prognostic outcomes, and it promotes cancer invasion, metastasis, and uncontrolled cell proliferation [5]. In bone regeneration, Mg2+-induced upregulation of Trpm7 in macrophages during the early inflammation phase contributes to the formation of a pro-osteogenic immune microenvironment, while continued Mg2+ exposure in the later remodeling phase has negative effects on osteogenesis [6].

In conclusion, Trpm7 is essential for multiple biological functions including ion homeostasis and intracellular signaling. Studies using gene knockout models have shown its significance in various disease areas such as arthritis, cancer, and bone regeneration. Understanding Trpm7's functions through these models provides potential therapeutic targets for these diseases.

References:

1. Zhou, Renpeng, Chen, Yong, Li, Shufang, Ding, Changhai, Hu, Wei. 2022. TRPM7 channel inhibition attenuates rheumatoid arthritis articular chondrocyte ferroptosis by suppression of the PKCα-NOX4 axis. In Redox biology, 55, 102411. doi:10.1016/j.redox.2022.102411. https://pubmed.ncbi.nlm.nih.gov/35917680/

2. Zou, Zhi-Guo, Rios, Francisco J, Montezano, Augusto C, Touyz, Rhian M. 2019. TRPM7, Magnesium, and Signaling. In International journal of molecular sciences, 20, . doi:10.3390/ijms20081877. https://pubmed.ncbi.nlm.nih.gov/30995736/

3. Fleig, Andrea, Chubanov, Vladimir. . TRPM7. In Handbook of experimental pharmacology, 222, 521-46. doi:10.1007/978-3-642-54215-2_21. https://pubmed.ncbi.nlm.nih.gov/24756720/

4. Chubanov, Vladimir, Gudermann, Thomas. 2020. Mapping TRPM7 Function by NS8593. In International journal of molecular sciences, 21, . doi:10.3390/ijms21197017. https://pubmed.ncbi.nlm.nih.gov/32977698/

5. Wang, Zhi-Bin, Zhang, Xiu, Xiao, Fen, Wu, Nayiyuan, Wang, Jing. 2023. Roles of TRPM7 in ovarian cancer. In Biochemical pharmacology, 217, 115857. doi:10.1016/j.bcp.2023.115857. https://pubmed.ncbi.nlm.nih.gov/37839677/

6. Qiao, Wei, Wong, Karen H M, Shen, Jie, Cheung, Kenneth M C, Yeung, Kelvin W K. 2021. TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration. In Nature communications, 12, 2885. doi:10.1038/s41467-021-23005-2. https://pubmed.ncbi.nlm.nih.gov/34001887/