Life Sciences & Biomedicine Medicine, Research & Experimental Pharmacology & Pharmacy Research & Experimental Medicine Science & Technology
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.
Hsa-miR-605 regulates the proinflammatory chemokine CXCL5 in complex regional pain syndrome
Creators
Richa Pande - Drexel University
Ayush Parikh - Drexel University
Botros Shenoda - Drexel University
Sujay Ramanathan - Drexel University
Guillermo M. Alexander - Drexel University
Robert J. Schwartzman - Drexel University
Seena K. Ajit - Drexel University
Publication Details
Biomedicine & pharmacotherapy, v 140, pp 111788-111788
Publisher
Elsevier
Number of pages
7
Grant note
R01NS102836 / NIH NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
Resource Type
Journal article
Language
English
Academic Unit
Pharmacology and Physiology; [Retired Faculty]; Neurology
Web of Science ID
WOS:000670119700001
Scopus ID
2-s2.0-85107135817
Other Identifier
991019168895204721
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