Hypoxia Regulates MicroRNA Expression in the Human Carotid Body
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How hypoxia regulates gene expression in the human carotid body (CB) remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the impact of important post-transcriptional regulators, such as non-coding RNAs, and in particular miRNAs is not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins.
KeywordsCarotid body MicroRNA Hypoxia
Supported by research grants from the Research Council for Medicine, Sweden, Stockholm County Council, Thorsten Söderberg Research Foundation, Gösta Fraenckels Foundation, Jeanssons Foundation, Tore Nilsons Fundation, Magnus Bergvalls Foundation, Capio Foundation, LPS Medical, Karolinska Institutet Funds and The Swedish Society for Medicine, all from Stockholm, Sweden.
- Bishop T, Talbot NP, Turner PJ, Nicholls LG, Pascual A, Hodson EJ, Douglas G, Fielding JW, Smith TG, Demetriades M, Schofield CJ, Robbins PA, Pugh CW, Buckler KJ, Ratcliffe PJ (2013) Carotid body hyperplasia and enhanced ventilatory responses to hypoxia in mice with heterozygous deficiency of PHD2. J Physiol 591:3565–3577CrossRefGoogle Scholar
- Ortega-Saenz P, Pardal R, Levitsky K, Villadiego J, Munoz-Manchado AB, Duran R, Bonilla-Henao V, Arias-Mayenco I, Sobrino V, Ordonez A, Oliver M, Toledo-Aral JJ, Lopez-Barneo J (2013) Cellular properties and chemosensory responses of the human carotid body. J Physiol 591:6157–6173CrossRefGoogle Scholar
- Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179:5082–5089CrossRefGoogle Scholar