D’Elia, Arielle: vRAGE-ELP Fusion Protein for Diabetic Chronic Wounds

 

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Title:  unknown

Name: Arielle D’Elia

Major:  Biomedical Engineering

School affiliation: Douglass Residential College, School of Engineering

Programs: Aresty – Research or Conference Funding Recipient, The BME Research Scholars

Other contributors: Hwan June Kang and Dr. Francois Berthiaume

Abstract: Foot ulcers are a type of chronic non-healing wound commonly found in diabetic patients. About 25% of diabetic patients develop an ulcer, which is prone to further complications such as infection that may lead to amputation. Chronic skin wounds exhibit prolonged inflammation and high levels of proteases. We hypothesize that a major driver of the inflammation and proteolytic wound environment is the accumulation of advanced glycation end products (AGEs). AGEs are the product of proteins reacting with glucose under hyperglycemic conditions. When AGEs bind to their receptor, RAGE, they trigger proinflammatory gene expression, which impairs the wound healing process. We have successfully developed a fusion protein consisting of the v fragment of RAGE attached to 50 repeats of an elastin-like peptide (ELP), vRAGE-ELP, which acts as a competitive inhibitor for AGEs. By preventing AGE binding to RAGE on cells, we hypothesize that one can decrease pro-inflammatory gene expression. Here, we show that vRAGE-ELP fusion proteins bind to AGEs, thus inhibiting AGE-RAGE binding, as indicated by the decreased level of AGE-induced ICAM-1 expression on endothelial cells in vitro. Furthermore, vRAGE-ELP self-assembles into nanoparticles at 37ᵒC, which protects them from proteolytic degradation. We previously showed that vRAGE-ELP is bioactive at 37ᵒC both in vitro and in vivo. We are now investigating whether the bioactivity can be attributed to monomeric and/or nanoparticle forms of the protein. For this purpose, we use an ultrafiltration method to separate monomers from nanoparticles in solution.