Hypoxia regulates microRNA expression in the human carotid body

• Published in: Experimental cell research 2017-03, Vol.352 (2), p.412-419
• Main Authors: Mkrtchian, Souren, Lee, Kian Leong, Kåhlin, Jessica, Ebberyd, Anette, Poellinger, Lorenz, Fagerlund, Malin Jonsson, Eriksson, Lars I.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Adult; Aged; Aged, 80 and over; ANIMAL TISSUES; ANIMALS; ANOXIA; APOPTOSIS; BIOLOGICAL PATHWAYS; BIOLOGICAL RECOVERY; BRAIN; Carotid body; Carotid Body - metabolism; CELL DIFFERENTIATION; Cell Hypoxia; CELL PROLIFERATION; Cells, Cultured; GENES; HOMEOSTASIS; Humans; Hypoxia; Hypoxia - genetics; Hypoxia - metabolism; LEAD; Male; Medicin och hälsovetenskap; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; OXYGEN; Oxygen - metabolism; REGULATIONS; RESPONSE FUNCTIONS; RNA; SURGERY
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2017.02.027

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are 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. •Hypoxia triggers differential expression of many miRNAs in the human carotid body.•This can lead to the upregulation of proliferation and immune response functions.•CB expression profile in the carotid body resembles the miRNA expression pattern in the brain.•miRNAs are involved in the regulation of carotid body functions including oxygen sensing.