Effects of MCP-1 and TGF-beta on miR-106b-25 expression in immune cells
Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder occurring in an extremity after trauma. CRPS currently lacks an FDA-approved treatment. Circulating microRNA (miRNA) is a promising avenue to better understand disease mechanisms. miRNAs are short RNAs that can negatively regulate the translation of mRNA into proteins. Dysregulation in miRNA expression has downstream effects on cellular function that can contribute to disease. Our previous work identified miRNAs dysregulated in CRPS patients, including miR-25. In the genome, miR-25 occurs as a cluster of three miRNAs miR-106b, miR-93 and miR-25 (miR-106b-25 cluster). This study investigates how expression of this cluster in T cells and monocytes is affected by monocyte chemoattractant protein-1 (MCP-1/CCL2), a proinflammatory chemokine that is upregulated in CRPS patients. miR-25, miR-93, and miR-106b were detected by qPCR in both the Jurkat T-cell line and the THP-1 monocyte line. MCP-1 treatment significantly upregulated miR-25 expression in Jurkat T-cells and miR-93 and miR-106b in THP-1 monocytes. Our studies show T cells and monocytes could contribute to aberrant miR-25 expression in circulation under inflammation. We previously demonstrated that macrophage derived small extracellular vesicles (sEVs) can accelerate resolution of inflammatory pain and contain both TGFβ and miRNAs that can modulate TGFβ signaling. Current studies are examining how miR-106b-25 cluster expression in primary T cells and non-T cell splenocytes is affected by macrophage sEVs as a potential therapeutic. Preliminary results from this study indicate that sEV treatment can induce immune cell activation, change Tgfβ-I, Smad7, and Cd69 expression, and alter miRNA expression. Our findings will lay the groundwork for subsequent studies in primary immune cells and validation in an in vivo mouse model of CRPS, thereby strengthening translational and clinical relevance.
Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder occurring in an extremity after trauma. CRPS currently lacks an FDA-approved treatment. Circulating microRNA (miRNA) is a promising avenue to better understand disease mechanisms. miRNAs are short RNAs that can negatively regulate the translation of mRNA into proteins. Dysregulation in miRNA expression has downstream effects on cellular function that can contribute to disease. Our previous work identified miRNAs dysregulated in CRPS patients, including miR-25. In the genome, miR-25 occurs as a cluster of three miRNAs miR-106b, miR-93 and miR-25 (miR-106b-25 cluster). This study investigates how expression of this cluster in T cells and monocytes is affected by monocyte chemoattractant protein-1 (MCP-1/CCL2), a proinflammatory chemokine that is upregulated in CRPS patients. miR-25, miR-93, and miR-106b were detected by qPCR in both the Jurkat T-cell line and the THP-1 monocyte line. MCP-1 treatment significantly upregulated miR-25 expression in Jurkat T-cells and miR-93 and miR-106b in THP-1 monocytes. Our studies show T cells and monocytes could contribute to aberrant miR-25 expression in circulation under inflammation. We previously demonstrated that macrophage derived small extracellular vesicles (sEVs) can accelerate resolution of inflammatory pain and contain both TGFβ and miRNAs that can modulate TGFβ signaling. Current studies are examining how miR-106b-25 cluster expression in primary T cells and non-T cell splenocytes is affected by macrophage sEVs as a potential therapeutic. Preliminary results from this study indicate that sEV treatment can induce immune cell activation, change Tgfβ-I, Smad7, and Cd69 expression, and alter miRNA expression. Our findings will lay the groundwork for subsequent studies in primary immune cells and validation in an in vivo mouse model of CRPS, thereby strengthening translational and clinical relevance.