Msr1, also named CD204, is a key receptor mainly present on the surface of various macrophages. It plays essential roles in multiple pathophysiologic processes, especially in inflammation regulation. It is involved in pathways such as PI3K/AKT/GSK3β/β-catenin, JNK, and is associated with processes like lipid uptake and immune cell polarization [1,2,4]. Genetic models, like KO mouse models, have been crucial in studying its functions.

In KO mouse models, delayed intramembranous ossification was observed in Msr1 knockout mice compared to wild-type mice, indicating its role in promoting BMSC osteogenic differentiation and M2-like polarization via the PI3K/AKT/GSK3β/β-catenin pathway [1]. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, suggesting its role in lipid-induced inflammation in non-alcoholic fatty liver disease [4]. Also, overexpression of Msr1 using F4/80-labelled AAV9 improved intrahepatic macrophage efferocytosis and promoted pro-resolving polarisation, ameliorating ischemia-reperfusion injury following aged-donor liver transplantation [3].

In conclusion, Msr1 is vital in inflammation and lipid-related processes. KO mouse models have revealed its significance in fracture repair, non-alcoholic fatty liver disease, and ischemia-reperfusion injury following aged-donor liver transplantation, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Zhao, Shu-Jie, Kong, Fan-Qi, Jie, Jian, Zhang, Han-Wen, Fan, Jin. 2020. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. In Theranostics, 10, 17-35. doi:10.7150/thno.36930. https://pubmed.ncbi.nlm.nih.gov/31903103/

2. Gudgeon, Jack, Marín-Rubio, José Luis, Trost, Matthias. 2022. The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer. In Frontiers in immunology, 13, 1012002. doi:10.3389/fimmu.2022.1012002. https://pubmed.ncbi.nlm.nih.gov/36325338/

3. Xu, Xue-Song, Liu, Tao, Chen, Ya-Jun, Cheng, Ming-Xiang, Li, Jin-Zheng. 2024. MSR1-dependent efferocytosis improved ischemia-reperfusion injury following aged-donor liver transplantation in mice by regulating the pro-resolving polarisation of macrophages. In Experimental cell research, 442, 114212. doi:10.1016/j.yexcr.2024.114212. https://pubmed.ncbi.nlm.nih.gov/39168433/

4. Govaere, Olivier, Petersen, Sine Kragh, Martinez-Lopez, Nuria, Trost, Matthias, Härtlova, Anetta. 2021. Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease. In Journal of hepatology, 76, 1001-1012. doi:10.1016/j.jhep.2021.12.012. https://pubmed.ncbi.nlm.nih.gov/34942286/