Blvra, known as biliverdin reductase A, is a pleiotropic enzyme that converts biliverdin-IX-alpha into the antioxidant and anti-nitrosative compound, bilirubin-IX-alpha [3]. It is involved in heme degradation pathway and has antioxidant properties against oxidative stress [1]. It is also associated with various cellular signaling pathways, and its biological importance lies in its potential roles in many physiological and pathological processes. Genetic models can be valuable for studying its functions.

In a Parkinson's disease (PD) animal model, the GK2-BLVRA fusion protein protected dopaminergic neuronal cells from oxidative stress, reduced reactive oxygen species production and DNA damage, suppressed MAPK activation, and modulated apoptosis-related protein expression levels [1]. In hepatocellular carcinoma (HCC) cell lines, knockdown of Blvra suppressed cell proliferation, invasion, migration, and induced apoptosis, while also blocking the activation of the Wnt/β-catenin pathway [2]. Similarly, in colorectal cancer, Blvra overexpression increased cell proliferation, migration, invasion, augmented EMT, and hindered apoptosis through activating the Wnt/β-catenin signaling pathway, and knockdown of Blvra showed opposite effects [3]. In a germinal matrix hemorrhage rat model, Blvra triggered a signaling cascade that ameliorated post-hemorrhagic neurological deficits, inhibited TLR4 expression, and induced up-regulation of CD36 scavenger receptor level to enhance hematoma resolution [4].

In conclusion, Blvra has important functions in antioxidant defense, cell growth, and apoptosis regulation. Model-based research, such as in PD, HCC, colorectal cancer, and germinal matrix hemorrhage models, has revealed its role in these disease-related biological processes. These findings contribute to understanding the mechanisms of these diseases and may provide potential therapeutic targets related to Blvra.

References:

1. Choi, Yeon Joo, Kwon, Hyun Jung, Shin, Min Jea, Eum, Won Sik, Choi, Soo Young. 2023. Protective effect of GK2 fused BLVRA protein against oxidative stress-induced dopaminergic neuronal cell damage. In The FEBS journal, 290, 2923-2938. doi:10.1111/febs.16721. https://pubmed.ncbi.nlm.nih.gov/36688733/

2. Chen, Xinju, Yang, Fangming, Zhang, Chuanlei, Chen, Xiaoqi, Zhao, Wenxia. 2024. BLVRA exerts its biological effects to induce malignant properties of hepatocellular carcinoma cells via Wnt/β-catenin pathway. In Journal of molecular histology, 55, 159-167. doi:10.1007/s10735-023-10179-w. https://pubmed.ncbi.nlm.nih.gov/38216836/

3. Mao, Haiyan, Xu, Yuan, Zhang, Zhengrong, Liu, Siping, Bo, Ping. 2020. Biliverdin Reductase A (BLVRA) Promotes Colorectal Cancer Cell Progression by Activating the Wnt/β-Catenin Signaling Pathway. In Cancer management and research, 12, 2697-2709. doi:10.2147/CMAR.S242531. https://pubmed.ncbi.nlm.nih.gov/32425592/

4. Zhang, Yiting, Ding, Yan, Lu, Tai, Tang, Jiping, Zhang, John H. 2017. Bliverdin reductase-A improves neurological function in a germinal matrix hemorrhage rat model. In Neurobiology of disease, 110, 122-132. doi:10.1016/j.nbd.2017.11.017. https://pubmed.ncbi.nlm.nih.gov/29203281/