Mc5r, the melanocortin 5 receptor, is a G protein-coupled receptor (GPCR) expressed in terminally differentiated sebaceous glands [1]. It has been implicated in multiple biological functions such as exocrine gland function, lipid metabolism, immune response, and energy metabolism [1,5]. MC5R may be involved in pathways like PI3K/AKT, MAPK, and those related to glycolipid metabolism [3,5]. Genetic models, especially knockout mouse models, are valuable for studying its functions.

In MC5R-deficient mice, several phenotypes were observed. In skin, MC5R -/- mice showed increased sensitivity to UVB waves, with skin ulcers and severe inflammation at lower UVB doses compared to wild-type mice, along with increased transepidermal water loss, indicating a decreased skin barrier function [4]. In hematopoietic function, MC5R deficiency aggravated irradiation-induced myelosuppression due to impaired proliferation and reconstitution of hematopoietic stem cells (HSCs), suggesting that the melanocortin/MC5R axis is crucial for regulating HSC proliferation under stress [3]. Also, in the context of cancer, the pituitary hormone α-MSH acts on bone marrow progenitors through MC5R to promote myelopoiesis, myeloid cell accumulation, immunosuppression, and tumor growth, and MC5R peptide antagonist can boost antitumor immunity [2].

In conclusion, MC5R plays essential roles in maintaining skin barrier function, regulating hematopoietic stem cell proliferation under stress, and influencing tumor-related immune responses. The study of MC5R knockout mouse models has provided significant insights into its functions in these biological processes and disease-related conditions, contributing to our understanding of the underlying mechanisms and potentially paving the way for new therapeutic strategies in skin, hematopoietic, and cancer-related diseases. [2,3,4]

References:

1. Liu, Jian, Shu, Mingrong, Liu, Shaobo, Pu, Dan, Deng, Cheng. 2022. Differential MC5R loss in whales and manatees reveals convergent evolution to the marine environment. In Development genes and evolution, 232, 81-87. doi:10.1007/s00427-022-00688-1. https://pubmed.ncbi.nlm.nih.gov/35648215/

2. Xu, Yueli, Yan, Jiaxian, Tao, Ye, Jiang, Wei, Zhou, Rongbin. 2022. Pituitary hormone α-MSH promotes tumor-induced myelopoiesis and immunosuppression. In Science (New York, N.Y.), 377, 1085-1091. doi:10.1126/science.abj2674. https://pubmed.ncbi.nlm.nih.gov/35926007/

3. Chen, Naicheng, Quan, Yong, Chen, Mo, Wang, Junping, Hu, Mengjia. . Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury. In Blood advances, 7, 3199-3212. doi:10.1182/bloodadvances.2022009249. https://pubmed.ncbi.nlm.nih.gov/36920787/

4. Shintani, Akari, Sakata-Haga, Hiromi, Moriguchi, Keiichi, Mochizuki, Takashi, Hatta, Toshihisa. 2021. MC5R Contributes to Sensitivity to UVB Waves and Barrier Function in Mouse Epidermis. In JID innovations : skin science from molecules to population health, 1, 100024. doi:10.1016/j.xjidi.2021.100024. https://pubmed.ncbi.nlm.nih.gov/34909724/

5. Zhang, Jinqi, Xing, Ya, Li, Fangbo, Gong, Daoqing, Geng, Tuoyu. 2023. Study on the Mechanism of MC5R Participating in Energy Metabolism of Goose Liver. In International journal of molecular sciences, 24, . doi:10.3390/ijms24108648. https://pubmed.ncbi.nlm.nih.gov/37239994/