Hsa-miR-605 regulates the proinflammatory chemokine CXCL5 in complex regional pain syndrome - 17/06/21
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Abstract |
Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by inflammation and debilitating pain. CRPS patients with pain refractory to more conventional analgesics can be treated with subanesthetic doses of ketamine. Our previous studies found that poor responders to ketamine had a 22-fold downregulation of the miRNA hsa-miR-605 in blood prior to ketamine treatment. Hence, we sought to investigate the functional significance of miR-605 downregulation and its impact on target gene expression, as investigating target mRNAs of differentially expressed miRNAs can provide important insights on aberrant gene expression that may contribute to disease etiology. Using a bioinformatics prediction, we identified that miR-605 can target the proinflammatory chemokine CXCL5, which plays a role in leukocyte recruitment and activation. We hypothesized that downregulation of miR-605 in poor responders to ketamine could increase CXCL5 expression and thereby contribute to inflammation in these patients. We confirmed that miR-605 regulates CXCL5 by using a miRNA mimic and inhibitor in human primary endothelial cells. Inhibition of miR-605 increased CXCL5 secretion and migration of human monocytic cells, thereby demonstrating a functional impact of miR-605 on chemotaxis. Additionally, CXCL5 mRNA was upregulated in whole blood from poor responders to ketamine, and CXCL5 protein was increased in plasma from CRPS patients. Thus, our studies suggest that miR-605 regulation of CXCL5 can regulate inflammation.
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Highlights |
• | CRPS patients responding poorly to ketamine -have lower miR-605 in whole blood. |
• | miR-605 is predicted to target proinflammatory chemokine CXCL5. |
• | miR-605 binds to CXCL5 decreasing CXCL5 mRNA and protein expression in vitro. |
• | miR-605 regulates leukocyte migration via CXCL5 impacting chemotaxis in vitro. |
• | CRPS patients show increased CXCL5 mRNA and protein expression in whole blood. |
Abbreviations : ANOVA, CRHR1, CRPS, CXCL5, CXCR2, DMEM, ELISA, ENA78/CXCL5, FBS, HEK293, HUVEC, IL-6, KO, LPS, miRNA, NFκB2, NMDA, NOS2A or iNOS, rhTNFα, STAT3, UDP, UGT1A1, UVB, VEGFA, 3′UTR
Keywords : miR-605, CXCL5, Complex regional pain syndrome, Pain, Inflammation, miRNA
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Vol 140
Article 111788- août 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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