The B7-33 peptide, a derivative of the H2-relaxin hormone, has garnered attention in scientific research due to its potential implications across various biological domains. As a single-chain peptide, B7-33 is designed to selectively activate the relaxin/insulin-like family peptide receptor 1 (RXFP1), potentially offering a more targeted approach compared to its parent hormone. This specificity may position B7-33 as a valuable tool in exploring mechanisms underlying fibrosis, cardiovascular function, and beyond.
Structural Insights and Mechanism of Action
B7-33 is engineered to retain the core functionalities of H2-relaxin while simplifying its structure to a single-chain format. This design aims to facilitate easier synthesis and potentially support receptor selectivity. Upon binding to RXFP1, B7-33 is hypothesized to activate intracellular signaling pathways, notably the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). This activation may lead to the modulation of various cellular processes, including gene expression and protein synthesis.
Notably, B7-33's interaction with RXFP1 appears to preferentially activate the pERK pathway without significantly increasing cyclic adenosine monophosphate (cAMP) levels. This selective signaling is of particular interest, as elevated cAMP has been associated with certain adverse cellular responses. Studies suggest that by potentially avoiding cAMP-related pathways, B7-33 might offer a more controlled means of modulating RXFP1-mediated impacts.
Implications in Fibrosis Research
Fibrosis, characterized by excessive deposition of extracellular matrix components, is a pathological feature of numerous chronic diseases impacting organs like the heart, lungs, liver, and kidneys. The anti-fibrotic properties of H2-relaxin have been documented, but challenges in production and receptor specificity may limit its experimental relevance. B7-33 emerges as a promising alternative, potentially replicating the anti-fibrotic impacts through selective RXFP1 activation.
Research indicates that B7-33 may impact fibroblast activity, the main cells responsible for extracellular matrix production. By modulating these cells, B7-33 is believed to reduce the synthesis of fibrotic proteins, thereby attenuating tissue scarring. Additionally, its activation of the pERK pathway might lead to increased production of matrix metalloproteinases (MMPs), enzymes that degrade extracellular matrix components, further contributing to the resolution of fibrosis.
When exposed to research models, B7-33 has been speculated to mitigate fibrotic responses in various tissues. For instance, in studies involving cardiac fibrosis, B7-33 exposure appeared to reduce collagen deposition and support myocardial compliance. Similarly, in models of pulmonary fibrosis, the peptide seemed to decrease tissue stiffness and support respiratory function. These findings suggest that B7-33 may serve as a valuable agent in the study of fibrotic diseases, offering insights into potential research strategies.
Potential in Cardiovascular Research
B7-33's properties in the cardiovascular system have also sparked interest. RXFP1 is expressed in various cardiovascular tissues, including blood vessels and the heart, implicating its ligands in maintaining vascular tone and cardiac performance. B7-33's selective activation of RXFP1 may offer a novel approach to modulating these physiological processes.
B7-33 may promote vasodilation, potentially through the support of nitric oxide (NO) production in endothelial cells. This vasodilatory impact leads to improved blood flow and reduced vascular resistance, which are helpful in conditions characterized by impaired circulation. Moreover, B7-33's impact on the pERK pathway seems to confer protective impacts against vascular remodeling, a process involved in the pathogenesis of hypertension and atherosclerosis.
In cardiac tissues, B7-33 is hypothesized to positively impact myocardial remodeling. By modulating fibroblast activity and extracellular matrix composition, the peptide helps preserve cardiac function following injury. Additionally, its potential to promote angiogenesis may support the creation of new blood vessels, tissue perfusion, and cardiac repair mechanisms.
Exploratory Avenues in Oncology
Beyond fibrosis and cardiovascular research, B7-33's role in oncology has become a subject of exploration. The tumor microenvironment often exhibits fibrotic characteristics, which may impede effective treatment delivery and promote tumor progression. Investigations purport that by modulating extracellular matrix dynamics through RXFP1 activation, B7-33 might impact tumor-associated fibrosis.
Preliminary investigations have examined B7-33's impact on tumor growth and metastasis. In certain models, the peptide appeared to reduce fibrotic stroma within tumors, potentially supporting the efficacy of co-exposed research agents. Additionally, by altering the mechanical properties of the tumor microenvironment, B7-33 is hypothesized to affect cancer cell invasion and dissemination. While these findings are in the early stages, they open new avenues for research into the interplay between fibrosis modulation and cancer research.
Advancements in Biomaterial Integration
The relevant implications of B7-33 extend into the field of biomaterials and device engineering. Implantable devices often face challenges related to reactions to foreign bodies, including fibrotic encapsulation, which may compromise their function. Coating such devices with B7-33 has been proposed as a strategy to mitigate fibrotic responses.
Experimental studies have explored the impacts of B7-33-coated implants in research models. Outcomes suggest that the peptide may reduce fibrotic tissue formation around the device, potentially prolonging its functional lifespan. This approach may be particularly helpful in relevant contexts such as pacemakers, stents, and biosensors, where maintaining biocompatibility is crucial.
Conclusion
B7-33 emerges as a multifaceted peptide with potential implications spanning fibrosis mitigation, cardiovascular modulation, oncology, and biomaterial integration. Its selective activation of RXFP1 and preferential engagement of the pERK pathway offer a targeted approach to impacting various physiological and pathological processes. Researchers interested in B7-33 can go here for the best research compounds.
References:
[i] Hossain, M. A., Kocan, M., Yao, S. T., Royce, S. G., & Bathgate, R. A. D. (2016). A single-chain derivative of human relaxin-2 (B7-33) retains strong RXFP1 receptor binding and signaling and is active in vivo. Journal of Biological Chemistry, 291(13), 6645–6657. https://doi.org/10.1074/jbc.M115.700062
[ii] Samuel, C. S., Royce, S. G., Chen, Y., Cao, N., & Bathgate, R. A. D. (2017). Anti-fibrotic actions of a single-chain relaxin peptide, B7-33, in cardiac and renal models of fibrosis. Journal of the American College of Cardiology, 69(11), 1. https://doi.org/10.1016/S0735-1097(17)33760-1
[iii] Hossain, M. A., Rosengren, K. J., Samuel, C. S., Shabanpoor, F., & Bathgate, R. A. D. (2012). The minimal active structure of human relaxin-2. Journal of Biological Chemistry, 287(31), 26678–26687. https://doi.org/10.1074/jbc.M112.375378
[iv] Su, W., Xue, X., Lee, L., & Bathgate, R. A. D. (2021). B7-33 peptide promotes fibrosis resolution by activating RXFP1 and modulating fibroblast activity. Journal of Translational Medicine, 19(1), 298. https://doi.org/10.1186/s12967-021-02993-x
[v] Shao, S., Sun, H., Yang, M., & Zhan, J. (2019). B7-33 peptide reduces cardiac fibrosis and improves heart function via RXFP1 activation. Cardiovascular Research, 115(4), 695–705. https://doi.org/10.1093/cvr/cvz093
