C5AR1 Specific Neutra™ Antibody Products

Complement C5a Receptor 1 (C5AR1) facilitates G protein-coupled receptor activity which is found in the apical region of cells and the basolateral plasma membrane. This receptor plays a role in various processes such as the complement component C5a signaling pathway, mRNA transcription via RNA polymerase II, and the upregulation of the ERK1 and ERK2 cascade. C5AR1 acts as a biomarker for Alzheimer's disease and is linked to conditions such as mast-cell sarcoma and hypersensitivity reaction type III disease.

Its Gene ID: 728, UniProtKB ID: P21730, and OMIM ID: 113995.

C5AR1 Signaling Pathway

C5AR1 is a classic seven-transmembrane G protein-coupled receptor mainly found on the cell surface, where it facilitates signal transduction via Gα family proteins. Subsequent signaling through the PI3K or Ras MAPK pathways influences cell growth, motility, metabolism, survival, and cytokine production. In contrast, C5AR2 preferentially signals through β-arrestins, leading to the activation of the transcription factor NF-κB. C5AR1 and C5AR2 can also form heteromers and recruit β-arrestins.

Fig.1 C5A receptors related signaling pathway.^{1, 4}

Applications of Anti-C5AR1 Antibodies

• Anti-C5AR1 Antibody Reveals Role of C5AR in Dental Nerve Regeneration

Given the critical role of sensory innervation in maintaining tooth vitality, identifying signals that regulate nerve regeneration, and the resulting cellular events is crucial. The complement system, a key player in innate immunity and inflammation becomes activated at the site of injury in human carious teeth and significantly contributes to dental-pulp regeneration through the interaction of the active Complement C5a fragment with pulp progenitor cells. To elucidate the role of C5a in dental nerve regeneration, the expression of C5AR1 in both intact and carious tooth sections has been investigated. In intact tooth sections, minimal C5AR1 is observed in pulp tissue using immunohistochemistry by anti-C5AR1 antibody. Conversely, carious tooth sections exhibit strong C5AR1 immunoreactivity throughout the areas beneath the injury. These findings indicate a spatial correlation between C5AR1 expression and nerve sprouting in human carious teeth. Additionally, C5AR1 expression is upregulated in LTA-stimulated human pulp fibroblasts and under conditions of carious injury. By linking neurite outgrowth to human pulp fibroblasts through the activation of the complement system, these findings can inform the development of novel therapeutic approaches for early interventions targeting dentin-pulp regeneration.

Fig.2 Expression of C5AR1 in human pulp cells both in vivo and in vitro.^{2, 4}

• Anti-C5AR1 Antibody Reveals Its Role in Insulin Signaling Suppression in Skeletal Muscle

C5AR1 expression has been detected in skeletal muscle, a critical metabolic tissue and primary target for insulin. To assess the expression of C5AR1, lysates from human myoblasts and myotubes are analyzed via immunoblotting using a C5AR1 antibody, and the relative abundance of C5AR1 protein is determined. The findings have shown that C5a activates C5AR1, resulting in an acute suppression of insulin signaling in differentiated human skeletal muscle cells. Additionally, structurally diverse C5AR1 antagonists, along with genetic deletion effectively mitigate the suppression of insulin signaling by C5a in human skeletal myotubes. These results highlight the potential negative impact of heightened C5AR1 activation, typical in obesity and chronic inflammatory conditions, on insulin function in skeletal muscle cells. This indicates potential therapeutic opportunities to mitigate immune-driven insulin resistance in key peripheral metabolic tissues, including skeletal muscle.

Fig.3 Expression of C5AR1 in skeletal muscle by immunoblotting.^{3, 4}

Creative Biolabs presents an array of over 20 intricately engineered antibodies against C5AR1, crafted using recombinant methodologies. Furthermore, personalized customization services are available to tailor neutralizing antibodies directed at C5AR1 to exacting specifications.

REFERENCES

1. Trambas, Inez A., Melinda T. Coughlan, and Sih Min Tan. "Therapeutic potential of targeting complement C5a receptors in diabetic kidney disease." International Journal of Molecular Sciences 24.10 (2023): 8758.
2. Chmilewsky, Fanny, et al. "Nerve growth factor secretion from pulp fibroblasts is modulated by complement C5a receptor and implied in neurite outgrowth." Scientific reports 6.1 (2016): 31799.
3. Shah, Dinesh S., et al. "The C5AR1 complement receptor: A novel immunomodulator of insulin action in skeletal muscle." Cellular Signalling 113 (2024): 110944.
4. Distributed under Open Access license CC BY 4.0, without modification.