Lgr6, or leucine-rich repeat containing G protein-coupled receptor 6, is a receptor that has been implicated in multiple biological processes. It is associated with pathways such as Wnt signaling, which is crucial for cell growth, differentiation, and tissue homeostasis [4]. Lgr6 is important in stem cell-related functions and in the body's response to injury and disease. Genetic models, like knockout (KO) mouse models, have been instrumental in studying its functions.

In epidermal stem cells, Lgr6-marked cells have a nerve-dependent role in wound re-epithelialization. Ablation of Lgr6 stem cells delays wound healing, mimicking the effect of skin denervation, suggesting a key role for Lgr6 in the epidermal injury response [1]. In the heart, LGR6 knockout mice showed increased myocardial necroptosis after ischemia-reperfusion injury, indicating that LGR6 protects against this injury by suppressing necroptosis through the Wnt-STAT2/ZBP1 axis [2]. Also, in diabetic cardiomyopathy, LGR6 knockout aggravated cardiac dysfunction, ferroptosis, and mitochondrial disorders, while overexpression alleviated these effects via the STAT3/Pgc1a signaling pathway [3].

In conclusion, Lgr6 plays essential roles in processes like wound re-epithelialization, protecting the heart from ischemia-reperfusion injury, and alleviating diabetic cardiomyopathy. The use of Lgr6 KO mouse models has been vital in revealing these functions, providing insights into potential therapeutic strategies for skin wound healing, myocardial ischemia-reperfusion injury, and diabetic cardiomyopathy.

References:

1. Huang, Sixia, Kuri, Paola, Aubert, Yann, Capell, Brian C, Rompolas, Panteleimon. 2021. Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization. In Cell stem cell, 28, 1582-1596.e6. doi:10.1016/j.stem.2021.05.007. https://pubmed.ncbi.nlm.nih.gov/34102139/

2. Zhao, Mengmeng, Zheng, Zihui, Liu, Jianfang, Wan, Jun, Wang, Menglong. 2024. LGR6 protects against myocardial ischemia-reperfusion injury via suppressing necroptosis. In Redox biology, 78, 103400. doi:10.1016/j.redox.2024.103400. https://pubmed.ncbi.nlm.nih.gov/39471639/

3. Zhao, Mengmeng, Shen, Zican, Zheng, Zihui, Qin, Juan-Juan, Wang, Menglong. 2024. Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis. In Metabolism: clinical and experimental, 159, 155979. doi:10.1016/j.metabol.2024.155979. https://pubmed.ncbi.nlm.nih.gov/39038735/

4. Li, Tiancheng, Wang, Han, Jiang, Yukun, Li, Yuyu, Zou, Shujuan. 2023. LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling. In International journal of oral science, 15, 33. doi:10.1038/s41368-023-00237-0. https://pubmed.ncbi.nlm.nih.gov/37558690/