Gprc5b, an orphan G-protein-coupled receptor, is involved in multiple biological processes. It has been associated with autophagy signaling, ion channel-related volume regulation, and pathways like AKT-mTOR-autophagy, NF-κB, and actin-MRTF-SRF. Gprc5b is crucial for normal physiological functions and its dysregulation is linked to various diseases, highlighting its potential as a therapeutic target [1,2,3,5,6].

In gene knockout studies, Gprc5b-deficient chondrocytes showed up-regulation of cartilage catabolic genes and down-regulation of anabolic genes in vitro. Mice lacking Gprc5b had a more severe osteoarthritis (OA) phenotype in a DMM-induced OA model, while overexpression alleviated cartilage degeneration [1]. In glomerular diseases, podocyte-specific Gprc5b knockout mice were partially protected from LPS-induced proteinuria and inflammatory cell recruitment, with Gprc5b regulating the inflammatory response via the NF-κB pathway [5]. In lymphatic development, Gprc5b-/-mice suffered from embryonic hydrops fetalis, hemorrhage, and attenuated lymphangiogenesis, and in cultured human LECs, Gprc5b was required for cell proliferation and viability [4].

In conclusion, Gprc5b is integral in biological processes such as cartilage metabolism, astrocyte volume regulation, lymphatic development, and inflammatory responses. Gene knockout mouse models have revealed its significant roles in diseases like osteoarthritis, genetic brain edema, glomerular diseases, and lymphatic-related conditions, offering insights into potential therapeutic strategies targeting Gprc5b for these diseases.

References:

1. He, Liang, Xu, Ziwei, Niu, Xin, Liu, Mingyao, Luo, Jian. 2023. GPRC5B protects osteoarthritis by regulation of autophagy signaling. In Acta pharmaceutica Sinica. B, 13, 2976-2989. doi:10.1016/j.apsb.2023.05.014. https://pubmed.ncbi.nlm.nih.gov/37521864/

2. Passchier, Emma M J, Kerst, Sven, Brouwers, Eelke, Min, Rogier, van der Knaap, Marjo S. . Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema. In Brain : a journal of neurology, 146, 3444-3454. doi:10.1093/brain/awad146. https://pubmed.ncbi.nlm.nih.gov/37143309/

3. Takizawa, Noburo, Hironaka, Takanori, Mae, Kyosuke, Nagasaka, Akiomi, Nakaya, Michio. 2021. GPRC5B promotes collagen production in myofibroblasts. In Biochemical and biophysical research communications, 561, 180-186. doi:10.1016/j.bbrc.2021.05.035. https://pubmed.ncbi.nlm.nih.gov/34023784/

4. Xu, Wenjing, Nelson-Maney, Nathan P, Bálint, László, St Croix, Brad, Caron, Kathleen M. 2022. Orphan G-Protein Coupled Receptor GPRC5B Is Critical for Lymphatic Development. In International journal of molecular sciences, 23, . doi:10.3390/ijms23105712. https://pubmed.ncbi.nlm.nih.gov/35628521/

5. Zambrano, Sonia, Möller-Hackbarth, Katja, Li, Xidan, Lal, Mark, Patrakka, Jaakko. 2019. GPRC5b Modulates Inflammatory Response in Glomerular Diseases via NF-κB Pathway. In Journal of the American Society of Nephrology : JASN, 30, 1573-1586. doi:10.1681/ASN.2019010089. https://pubmed.ncbi.nlm.nih.gov/31285284/

6. Freundt, Greta Verena, von Samson-Himmelstjerna, Friedrich Alexander, Nitz, Jan-Thorge, Preusch, Michael, Hippe, Hans-Jörg. 2022. The orphan receptor GPRC5B activates pro-inflammatory signaling in the vascular wall via Fyn and NFκB. In Biochemical and biophysical research communications, 592, 60-66. doi:10.1016/j.bbrc.2022.01.009. https://pubmed.ncbi.nlm.nih.gov/35033869/