Cbr2-KO Mouse

Cbr2, also known as NADH-Cytochrome B5 reductase 2, is involved in multiple biological processes. It has been implicated in angiogenesis, and is part of the endocannabinoid system where cannabinoid receptors CBR1 and CBR2 interact with cannabinoids and play roles in various physiological functions such as appetite, pain, sleep, and mood regulation [1,2,3].

In the context of diabetic retinopathy, Cbr2 expression was significantly downregulated in diabetic rat retinas and high-glucose-stimulated human retinal microvascular endothelial cells. Intravitreal injection of CBR2-expressing lentivirus reduced retinal angiogenesis, acellular capillary formation, and pericyte loss, along with decreased expression of hypoxia-inducible factor-1α (HIF-1α), cluster of differentiation 31 (CD31), and vascular endothelial growth factor A (VEGFA), suggesting that Cbr2 might alleviate retinal vascular dysfunction by regulating VEGFA [1]. In breast cancer, nuclear CBR2 was negatively correlated with grade and positively correlated with estrogen receptor and progesterone receptor-positive status, while high cytoplasmic expression of CBR2 was associated with increased locoregional and distant recurrences, though not reaching statistical significance [2]. In preterm birth, the expression of CBR2 in the placenta was significantly lower in women after preterm birth compared to term births, indicating that decreased CBR2 expression could serve as an indicator in predicting preterm birth [4].

In conclusion, Cbr2 plays important roles in angiogenesis, and its dysregulation is associated with diseases such as diabetic retinopathy, breast cancer, and preterm birth. These findings from in vivo and clinical-related studies contribute to understanding the biological functions of Cbr2 and its potential as a biomarker or therapeutic target in these disease areas.

References:

1. Chen, Jun, Sun, Yizhou, Chen, Lei, Zhou, Yun. 2022. NADH-Cytochrome B5 reductase 2 suppresses retinal vascular dysfunction through regulation of vascular endothelial growth factor A in diabetic retinopathy. In Experimental eye research, 222, 109186. doi:10.1016/j.exer.2022.109186. https://pubmed.ncbi.nlm.nih.gov/35820466/

2. Morin-Buote, Jessica, Ennour-Idrissi, Kaoutar, Poirier, Éric, Durocher, Francine, Diorio, Caroline. 2021. Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients. In Journal of personalized medicine, 11, . doi:10.3390/jpm11090852. https://pubmed.ncbi.nlm.nih.gov/34575629/

3. Santos, Ivan, P P Oliveira, M Beatriz, Casas, Ana, Fidalgo, Javier, Almeida, Hugo. 2024. Understanding the Potential of CBD for Health Benefits: an Overview. In Current drug discovery technologies, , . doi:10.2174/0115701638305553240529103622. https://pubmed.ncbi.nlm.nih.gov/38847170/

4. Feduniw, Stepan, Krupa, Izabela, Łagowska, Katarzyna, Stawarz, Barbara, Raba, Grzegorz. 2024. Placental Cannabinoid Receptor Expression in Preterm Birth. In Journal of pregnancy, 2024, 6620156. doi:10.1155/2024/6620156. https://pubmed.ncbi.nlm.nih.gov/38745869/