Characterizing an Alternatively Spliced Variant of Chemokine Receptor 2 in Painful Diabetic Neuropathy

Abstract

Prior research efforts have demonstrated a link between neuroinflammation and the progres-sion of Painful Diabetic Neuropathy (PDN), a chronic cascade of nerve damage that presents as tingling, numbness, hypersensitivity to touch, or intense pain. Current treatments are focused on pain manage-ment, serving to temporarily mask these symptoms without repressing or slowing nerve damage. The chemokine-receptor system has been closely stud-ied for its role in perpetuating neuropathic pain, alt-hough its precise mechanistic involvement remains unclear due to the network’s complexity. Because of its likely role in regulating neuropathic pain, target-ing CCR2 may be the key to effective treatment of PDN.Alternative splicing of CCR2 leads to two dis-tinct isoforms with different C-terminus sequences, CCR2A and CCR2B. The present study was intended to differentiate between these isoforms through spe-cific primer design, selection of optimized pairs, RT-PCR, and amplicon sequencing to verify the PCR products. However, the study has revealed a third, previously unreported isoform, CCR2C, due to evi-dence of alternative splicing and both the absence and insertion of parts of A and B. In the long term, we predict that the relationship between CCR2’s alternatively spliced transcript variants will lead to a distinct pattern of isoform prevalence in individuals suffering from PDN. Discerning the genetic profiles of patients with PDN and healthy individuals will clar-ify the complex mechanism driving CCR2’s intracel-lular interactions and offer more effective therapeu-tic options.