The recombinant human RSPO1 protein is expressed in mammalian cells. Its expression region corresponds to the 31-263aa of the human RSPO1. It is fused with a 10xHis-Avi-tag at the C-terminus. The resulting recombinant RSPO1 protein is extracted after cell lysis and purified with affinity chromatography. SDS-PAGE confirms its purity above 95%, and the LAL method ensures its endotoxin levels are below 1.0 EU/μg. It is validated to be an active protein. Functional ELISA validates its binding to the human LGR5 (CSB-MP012906HU1), with an EC50 of 124.0-174.1 ng/mL.
Human RSPO1 is a member of the R-spondin family of secreted proteins, which play critical roles in enhancing Wnt signaling pathways, particularly the Wnt/β-catenin pathway. RSPO1 is known for its ability to stabilize β-catenin, a key effector in Wnt signaling, thereby promoting various biological processes including cell proliferation, differentiation, and tissue homeostasis [1][2]. RSPO1 is characterized by two furin-like repeats and a thrombospondin type 1 repeat, which are essential for its signaling activity [3][4].
RSPO1 is expressed in various tissues, including the intestine and gonads, and has been implicated in developmental processes such as ovarian development and nephron progenitor maintenance [5][6][7]. Its expression is particularly significant during early ovarian development, where it augments β-catenin signaling, suggesting a role in sexual differentiation [5][7]. Furthermore, mutations in the RSPO1 gene have been associated with disorders of sex development, including cases of male-to-female sex reversal [8][9].
RSPO1 has been shown to influence keratinocyte proliferation and differentiation, making it relevant in the context of skin cancers such as squamous cell carcinoma [10][11]. Moreover, RSPO1's interaction with other proteins, such as LGR4 and LGR5, facilitates its signaling capabilities, linking it to various cellular responses and potentially to tumorigenesis [11][12].
Recent studies have also explored the role of RSPO1 in metabolic processes, particularly its association with obesity and insulin resistance [13][14]. Additionally, RSPO1 has been identified as a protective factor against radiation-induced gastrointestinal damage, further emphasizing its significance in tissue repair and regeneration [15][16].
References:
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[11] A. Glinka, C. Dolde, N. Kirsch, Y. Huang, O. Kazanskaya, D. Ingelfinger, et al. Lgr4 and lgr5 are r‐spondin receptors mediating wnt/β‐catenin and wnt/pcp signalling, Embo Reports, vol. 12, no. 10, p. 1055-1061, 2011. https://doi.org/10.1038/embor.2011.175
[12] X. Gong, K. Carmon, Q. Lin, A. Thomas, J. Yi, & Q. Liu. Lgr6 is a high affinity receptor of r-spondins and potentially functions as a tumor suppressor, Plos One, vol. 7, no. 5, p. e37137, 2012. https://doi.org/10.1371/journal.pone.0037137
[13] Y. Kang, J. Kim, H. Yi, K. Joung, H. Kim, & B. Ku. Serum r-spondin 1 is a new surrogate marker for obesity and insulin resistance, Diabetes & Metabolism Journal, vol. 43, no. 3, p. 368, 2019. https://doi.org/10.4093/dmj.2018.0066
[14] O. BAŞPINAR>, Y. Simsek, D. Kocer, O. Dizdar, & H. Does Serum R-Spondin-1 Play a Role in PCOS Pathophysiology? Genel Tıp Dergisi, vol. 32, no. 5, p. 490-493, 2022. https://doi.org/10.54005/geneltip.1111079
[15] P. Bhanja, S. Saha, R. Kabarriti, L. Liu, N. Roy‐Chowdhury, J. Roy‐Chowdhury, et al. Protective role of r-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice, Plos One, vol. 4, no. 11, p. e8014, 2009. https://doi.org/10.1371/journal.pone.0008014
[16] J. Zhao, K. Kim, J. Vera, S. Palencia, M. Wagle, & A. Abo. R-spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical wnt/β-catenin pathway, Proceedings of the National Academy of Sciences, vol. 106, no. 7, p. 2331-2336, 2009. https://doi.org/10.1073/pnas.0805159106
